chondroitin-sulfates and Osteoarthritis

The purpose of the review of scientific medical literature was to evaluate the data of the epidemiology of osteoarthritis (OA) and cardiovascular diseases (CVD) with the analysis of risk factors, pathophysiological and pathobiochemical mechanisms of the relationship between OA and the risk of developing CVD in the presence of chronic pain, modern strategies for screening and management of this cohort of patients, the mechanism of action and pharmacological effects of chondroitin sulfate (CS). Conclusions were drawn about the need for additional clinical and observational studies of the efficacy and safety of the parenteral form of CS (Chondroguard) in patients with chronic pain in OA and CVD, improvement of clinical recommendations for the treatment of chronic pain in patients with OA and cardiovascular risk, with special attention to interventions that eliminate mobility restrictions in patients and the inclusion of basic and adjuvant therapy with DMOADs to achieve the goals of multipurpose monotherapy in patients with contraindications to standard therapy drugs.. Обзора — оценка данных об эпидемиологии остеоартрита (ОА) и сердечно-сосудистых заболеваний (ССЗ) с анализом факторов риска, патофизиологических и патобиохимических механизмов связи ОА и риска развития ССЗ при хронической боли, в том числе боли в спине, современных стратегий ведения данной когорты пациентов. Анализируются механизмы фармакологических эффектов хондроитина сульфата (ХС). Сделаны выводы о необходимости проведения дополнительных клинических исследований эффективности и безопасности применения парентеральной формы ХС (Хондрогард) у пациентов с хронической болью при ОА и ССЗ. Актуальной является проблема проведения вмешательств, устраняющих ограничения подвижности пациентов, с включением режимов базовой и вспомогательной терапии препаратами, изменяющими течение заболевания, у пациентов с противопоказаниями к приему нестероидных противовоспалительных препаратов.

Topics: Cardiovascular Diseases; Chondroitin Sulfates; Chronic Pain; Combined Modality Therapy; Humans; Osteoarthritis

Animal origin chondroitin sulfate is employed as anti-inflammatory drug and food supplement against anti-osteoarthritis, but also as antioxidant, antitumor, anticoagulant, and immune-regulatory agent or as biomaterial in tissue engineering scaffolds and in drug-delivery systems. As its biological properties depend on the structural characteristics, multi-analytical approaches are necessary to correlate specific features of its heterogenic composition to the different bioactivities. This is of paramount importance to assess the efficacy of pharmaceuticals and food supplements, beyond safety quality control. This review would address the issue of chondroitin sulfate characterization according to the Pharmacopeia testing monograph point of view giving an update of the analytical novelties reported in the last ten years that might be employed for the product testing and releasing on the market. Not-instrumental (e.g. colorimetric assays) and instrumental techniques, most of them coupling diverse chromatographic separation methods with spectroscopic and spectrometry detection techniques, mono and bi-dimensional NMR approaches, are compared as tools to evaluate identity, titer, purity grade, monosaccharide and disaccharide composition, averaged molecular weight and viscosity, charge and sulfate content, impurities and related substances including the presence of other glycosaminoglycans.

Topics: Animals; Anticoagulants; Chondroitin Sulfates; Dietary Supplements; Glycosaminoglycans; Keratan Sulfate; Osteoarthritis

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Economics, Pharmaceutical; Humans; Knee Joint; Osteoarthritis; Osteoarthritis, Knee; Treatment Outcome

Chondroitin sulfate (CS) belongs to a class of molecules called glycosaminoglycans (GAGs). These are long, linear chains of polysaccharides comprising alternating amino sugars and hexuronic acid. Similar to other GAGs, CS is important in a multitude of biological activities. Alteration of CS levels has been implicated in several pathological conditions, including osteoarthritis (OA) and other inflammatory diseases, as well as physiological conditions, such as aging. Therefore, devising replenishment strategies for this molecule is an important area of research. In this review, we discuss the nature of CS, its function in different organs, and its implications in health and disease. We also describe different methods for the exogenous administration of CS.

Topics: Aging; Animals; Chondroitin Sulfates; Humans; Inflammation; Osteoarthritis

The article presents the data of the latest domestic and foreign original studies, the results of a number of meta-analyses, conclusions of randomized clinical trials (RCTs), and other scientific studies that prove the effectiveness and necessity of mandatory inclusion in the treatment of chronic pain syndrome of the stage of non-invasive non-pharmacological therapy. One of the promising areas of pharmacotherapy for degenerative-dystrophic joint lesions is the use of chondroprotectors (CP), in particular chondroitin sulfate (CS). According to new Clinical Recommendations of Ministry Health (MH) of the Russian Federation (RF) «Chronic pain in patients of elderly and senile age» (2020), according to which the purpose of CS is recommended for patients older than 60 years with joint pain and contraindications to non-steroidal anti-inflammatory drugs (NSAIDs) or senile asthenia for the purpose of pain relief and the prevention of exacerbations of pain. A high level of reliability and persuasiveness of the recommendations was noted (1A) of CS use. Most of the CS is available in the form of forms for oral use, the bioavailability of which, according to clinical studies, is 13-38% due to the destruction of the CS molecules in the gastrointestinal tract. Intramuscular (i/m) administration of the drug can increase the bioavailability of CS, which can not only increase the effectiveness of therapy, but also lead to a more rapid development of the symptomatic effect. In Russia available parenteral forms of CS (Chondroguard) pharmaceutical quality, efficacy has been proven in randomized clinical trial (RCT) MH RF. To relieve pain in the joints, it is recommended to use parenteral forms of CS (Chondroguard) at a dose of 100-200 mg per day, every other day, the total duration of the course of treatment is 25-30 injections.. В статье приведены данные последних отечественных и зарубежных оригинальных исследований, результаты ряда проведенных метаанализов, заключения рандомизированных клинических исследований (РКИ) и других научных публикаций, доказывающих эффективность и необходимость обязательного включения в терапию хронического болевого синдрома этапа неинвазивной нефармакологической терапии. Одним из перспективных направлений фармакотерапии дегенеративно-дистрофических поражений суставов является использование хондропротекторов, в частности, хондроитина сульфата (ХС). Согласно новым Клиническим рекомендациям Минздрава России «Хроническая боль у пациентов пожилого и старческого возраста» (2020), назначение ХС рекомендуется пациентам старше 60 лет с болью в суставах и противопоказаниями к нестероидным противовоспалительным препаратам или старческой астенией с целью купирования боли и профилактики обострений болевого синдрома. Отмечен высокий уровень достоверности и убедительности рекомендаций применения ХС (1А). Большая часть ХС выпускается в виде форм для перорального применения, биодоступность которых, по данным клинических исследований, составляет 13—38% вследствие разрушения молекул ХС в желудочно-кишечном тракте. Внутримышечное введение препарата позволяет увеличить биодоступность ХС, что может не только повысить эффективность терапии, но и привести к более быстрому развитию симптоматического эффекта. В РФ доступны парентеральные формы ХС (Хондрогард), эффективность которых доказана в РКИ, одобренном Минздравом России. Для купирования болевого синдрома в суставах рекомендуется использовать Хондрогард в дозировке 100—200 мг/сут, через день, общая продолжительность курса лечения составляет 25—30 инъекций. Для лиц пожилого возраста с остеоартритом различной локализации рекомендуется сохранять активный образ жизни, выполнять упражнения по лечебной физкультуре, программы пилатеса, пешие прогулки.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chronic Pain; Humans; Meta-Analysis as Topic; Middle Aged; Osteoarthritis; Randomized Controlled Trials as Topic; Russia

Osteoarthritis is one of the leading causes of a chronic pain in elderly people. Old and very old age in itself is a risk factor of a comorbidity, which often limits the therapy specified in clinical recommendations. First of all, it concerns NSAID. In such situations, priority is given to chondroitin sulfate (CS) and glucosamine sulfate (GS) having the anti-inflammatory properties comparable with effects of NSAID. CS and GS also promote the delay in progression of degenerative processes and restoration of the structure of cartilaginous tissue. The drugs of CS and GS groups are Chondroguard and Sustaguard Artro having the considerable evidence-based efficacy and safety and also a polymodality of effects in patients with a combination of osteoarthritis and socially important diseases (atherosclerosis, diabetes mellitus type 2, oncological diseases) and also geriatric syndromes (sarcopenia) and aging in general.. Остеоартрит - одна из ведущих причин хронического болевого синдрома у лиц пожилого возраста. Пожилой и старческий возраст сам по себе является фактором риска развития полиморбидности, которая зачастую ограничивает лекарственную терапию, указанную в клинических рекомендациях. Это прежде всего справедливо в отношении нестероидных противовоспалительных препаратов (НПВП). В таких ситуациях приоритетными становятся хондроитин сульфат (ХС) и глюкозамин сульфат (ГС), обладающие противовоспалительными свойствами, сравнимыми с эффектами НПВП. ХС и ГС также способствуют замедлению прогрессирования дегенеративных процессов и способствуют восстановлению структуры хрящевой ткани. Одними из препаратов ХС и ГС являются Хондрогард и Сустагард Артро, имеющие значительную доказательную базу в отношении эффективности и безопасности, а также полимодальности эффектов у пациентов с сочетанием остеоартрита и социально значимых заболеваний (атеросклероз, сахарный диабет 2-го типа, онкологические заболевания), а также гериатрических синдромов (саркопения) и старения в целом.

Topics: Aged; Chondroitin Sulfates; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Pain; Pain Management

Aging is an independent risk factor for the development of many diseases and geriatric syndromes. Osteoarthritis (OA), as the most common joint disease in the elderly, can be attributed to age - associated conditions. And the most significant geriatric syndrome, which dramatically affects the management and prognosis of an elderly, is frailty. The review provides current information on the prevalence of OA and frailty, their clinical and prognostic significance, and also shows the mutually aggravating role of these two conditions. The difference between non - and medication management of patients with OA and frailty is emphasized.. Клиническое значение и возможности терапии остеоартрита у больных старческой астенией Старение - самостоятельный фактор риска развития многих заболеваний и гериатрических синдромов. К возраст - ассоциированным состояниям можно отнести остеоартрит (ОА), как наиболее частое заболевание суставов в пожилом и старческом возрасте. А наиболее значимым гериатрическим синдромом, кардинально влияющим на тактику ведения и прогноз пожилого пациента, является старческая астения (СА). В обзоре представлены современные сведения о распространенности ОА и СА, их клинической и прогностической значимости, а также показана взаимно отягощающая роль этих двух состояний. Подчеркнута разница не - и медикаментозного ведения пациентов с ОА и СА.

Topics: Aged; Aged, 80 and over; Aging; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Chronic Pain; Frail Elderly; Frailty; Glucosamine; Humans; Osteoarthritis; Syndrome

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA and there is no effective treatment to stop its progression. Current pharmacologic treatments such as analgesics and non-steroidal anti-inflammatory drugs may improve the pain and offer some relief but they do not affect the progression of the disease. The chronic intake of these drugs may result in severe adverse events. The aim of this review is to revise the effects of nutrition on cartilage metabolism and OA progression.. A systematic literature search was performed including those related to macro- and micro-nutrients' actions on cartilage and OA outcome. We selected peer-reviewed articles reporting the results of human clinical trials.. Glucosamine and chondroitin sulfate have shown to delay OA knee progression in several clinical trials. The effectiveness of some products considered nutraceuticals has been widely reviewed in the literature. This article presents a general description of the effectiveness and mechanism of action of nutrients, vitamins, antioxidants and other natural components considered as part of the normal diet. Many in vitro studies indicate the efficacy of specific nutrients in cartilage metabolism and its involvement in OA. However, rigorous clinical studies needed to evaluate the efficacy of these compounds in humans are still missing. The influence of nutrients and diet on the metabolism of cartilage and OA could represent a long-term coadjuvant alternative in the management of patients with OA. Effects of diet modifications on lipid and cholesterol profiles, adequate vitamin levels and weight reduction in obese patients could influence the course of the disease.. This review demonstrates that nutrition can improve the symptoms of OA. Glucosamine and chondroitin sulfate have shown robustly to delay the progression of knee OA in several well-designed studies, however more controlled clinical trials are needed to conclude that nutritional changes slow down the progression of the disease.

Topics: Cartilage; Chondroitin Sulfates; Disease Progression; Glucosamine; Humans; Nutritional Status; Osteoarthritis; Vitamins

The industrial production of chondroitin sulfate (CS) uses animal tissue sources as raw material derived from different terrestrial or marine species of animals. CS possesses a heterogeneous structure and physical-chemical profile in different species and tissues, responsible for the various and more specialized functions of these macromolecules. Moreover, mixes of different animal tissues and sources are possible, producing a CS final product having varied characteristics and not well identified profile, influencing oral absorption and activity. Finally, different extraction and purification processes may introduce further modifications of the CS structural characteristics and properties and may lead to extracts having a variable grade of purity, limited biological effects, presence of contaminants causing problems of safety and reproducibility along with not surely identified origin. These aspects pose a serious problem for the final consumers of the pharmaceutical or nutraceutical products mainly related to the traceability of CS and to the declaration of the real origin of the active ingredient and its content. In this review, specific, sensitive and validated analytical quality controls such as electrophoresis, eHPLC (enzymatic HPLC) and HPSEC (high-performance size-exclusion chromatography) able to assure CS quality and origin are illustrated and discussed.

Topics: Animals; Chondroitin Sulfates; Dietary Supplements; Humans; Osteoarthritis

Topics: Acetylgalactosamine; Arthralgia; Chondroitin Sulfates; Humans; Osteoarthritis; Polysaccharides; Uronic Acids

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as "biosimilars" akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply.

Topics: Analgesics; Chondroitin Sulfates; Dietary Supplements; Drug Therapy, Combination; Europe; Glucosamine; Humans; Osteoarthritis; Osteoporosis; Societies, Medical

Osteoarthritis is the most prevalent chronic articular disease, in which pain is one of the main symptoms and the major determinant of functional loss. Several therapeutic options have been proposed, including chondroitin sulfate, but its actual usefulness has not yet been established. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified 13 systematic reviews including 50 randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether the use of chondroitin sulfate leads to an improvement in pain or functionality in osteoarthritis because the certainty of the evidence is very low.. La artrosis es la enfermedad articular crónica que presenta mayor prevalencia, en la cual el dolor es uno de los principales síntomas y el mayor determinante de la pérdida de funcionalidad. Se han planteado múltiples opciones terapéuticas, entre ellas el condroitín sulfato, pero su real utilidad aún no ha sido claramente demostrada. Para aclarar esta interrogante utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información. Identificamos 13 revisiones sistemáticas que en conjunto incluyen 50 estudios aleatorizados que responden la pregunta de este resumen. Extrajimos la información relevante, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si el uso de condroitín sulfato produce una mejoría en el dolor o la funcionalidad en la artrosis porque la certeza de la evidencia es muy baja.

Topics: Chondroitin Sulfates; Databases, Factual; Humans; Osteoarthritis; Pain; Randomized Controlled Trials as Topic

Drug administration by intra-articular injection is an emerging popular treatment for knee osteoarthritis (OA). This method of drug administration minimizes the toxic effects of the drugs administered systemically, and maximizes local effects. However, traditional oral drugs delivered via intra-articular injection are limited by the lack of sustained release. Injectable materials such as hydrogels or hydrogel microspheres have been extensively studied for their applications as intra-articular injection for the treatment of OA, which is attribute to their minimally invasive manner, extended drug retention time and high loading efficiency. In this review, we summarized hydrogel types and hydrogel characteristics for intra-articular injection, and the drugs, proteins and cells used in the injectable delivery systems. Through this review, we hope to inspire researchers to construct novel hydrogel-based delivery system for the intra-articular injection treatment of knee OA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chitosan; Chondroitin Sulfates; Drug Delivery Systems; Humans; Hyaluronic Acid; Hydrogels; Injections, Intra-Articular; Microspheres; Nanoparticles; Nanotechnology; Osteoarthritis; Steroids; Tissue Engineering

The purpose of this review is to highlight clinical research in osteoarthritis (OA). A literature search was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) with the search terms "osteoarthritis [All Fields] AND treatment [All Fields]" and the following limits activated: humans, English language, all adult 19+ years, published between April 1, 2014 and April 1, 2015. A second literature search was then conducted with the search terms "osteoarthritis [All Fields] AND epidemiology [All Fields]", with the same limits. Reports of surgical outcome, case series, surgical technique, tissue sample or culture studies, trial protocols, and pilot studies were excluded. Of 1523, 150 were considered relevant. Among epidemiologic and observational clinical studies, themes included physical activity, early knee OA, and confidence/instability/falls. Symptom outcomes of pharmacologic treatments were reported for methotrexate, adalimumab, anti-nerve growth factor monoclonal antibodies, strontium ranelate, bisphosphonates, glucosamine, and chondroitin sulfate, and structural outcomes of pharmacologic treatments for strontium ranelate, recombinant human fibroblast growth factor 18, and glucosamine and chondroitin sulfate. Symptom outcomes of non-pharmacologic interventions were reported for: neuromuscular exercise, quadriceps strengthening, weight reduction and maintenance, TENS, therapeutic ultrasound, stepped care strategies, cognitive behavior therapy for sleep disturbance, acupuncture, gait modification, booster physical therapy, a web-based therapeutic exercise resource center for knee OA; hip physical therapy for hip OA; and joint protection and hand exercises for hand OA. Structure outcomes of non-pharmacologic interventions were reported for patellofemoral bracing.

Topics: Adalimumab; Antirheumatic Agents; Arthroplasty, Replacement; Bone Density Conservation Agents; Chondroitin Sulfates; Cognitive Behavioral Therapy; Diphosphonates; Exercise Therapy; Glucosamine; Humans; Methotrexate; Osteoarthritis; Physical Therapy Modalities; Resistance Training; Thiophenes; Transcutaneous Electric Nerve Stimulation; Treatment Outcome; Ultrasonic Therapy

Some promising cartilage and synovium biomarkers are at various stages of development and awaiting further validation in larger patient populations with osteoarthritis (OA). Various reports have shown increased levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma) in such patients. The clinical value of these parameters in combination with imaging biomarkers in order to predict early onset and the burden of OA is being investigated. This review article aims to describe the potential usefulness of synovial and cartilage biomarkers for the diagnosis and prognosis of hemophilic arthropathy (HA) by using the existing literature on OA as an applicable model. A systematic review found that serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee OA and is sensitive to OA disease progression.

Topics: Biomarkers; Cartilage; Cartilage Oligomeric Matrix Protein; Chondroitin Sulfates; Collagen Type II; Humans; Osteoarthritis; Severity of Illness Index; Synovial Fluid

Osteoarthritis is a disabling affliction expected to increase in the coming decades, and disease- modifying osteoarthritis drugs (DMOADs) would be highly desirable adjuncts to symptomatic relief and structure reconstruction as they may delay the disease process. Chondroitin sulfate and glucosamine have been observed to exert beneficial effects on the metabolism of various cells involved in osteoarthritis as well as in animal models and clinical trials. Clinical trials have reported beneficial effects of both these biological agents, alone or in combination, on pain and functions as well as their structure-modifying capacity reported and analyzed in recent meta-analyses. Nonetheless, the effectiveness of these bioactive (macro)molecules as DMOADs reported from randomized trials is mismatched. Current studies with varying levels of evidence suggest that chondroitin sulfate and glucosamine can modify the disease progression but at the same time there are not absolute certainties on their efficacy in modifying the course of the disease. This comprehensive review aims to clarify the role of these compounds in the therapeutic molecules/ drugs useful to patients affected by osteoarthritis.

Topics: Animals; Anti-Inflammatory Agents; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

Chondroitin sulfate (CS) being a natural glycosaminoglycan is found in the cartilage and extracellular matrix. It shows clinical benefits in symptomatic osteoarthritis (OA) of the finger, knee, hip joints, low back, facial joints and other diseases due to its anti-inflammatory activity. It also helps in OA by providing resistance to compression, maintaining the structural integrity, homeostasis, slows breakdown and reduces pain in sore muscles. It is most often used in combination with glucosamine to treat OA. CS is a key role player in the regulation of cell development, cell adhesion, proliferation, and differentiation. Its commercial applications have been continuously explored in the engineering of biological tissues and its combination with other biopolymers to formulate scaffolds which promote and accelerate the regeneration of damaged structure. It is approved in the USA as a dietary supplement for OA, while it is used as a symptomatic slow-acting drug (SYSADOA) in Europe and some other countries. Any significant side effects or overdoses of CS have not been reported in clinical trials suggesting its long-term safety. This review highlights the potential of CS, either alone or in combination with other drugs, to attract the scientists engaged in OA treatment and management across the world.

Topics: Animals; Cell Adhesion; Cell Differentiation; Cell Proliferation; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

Osteoarthritis, a common joint disorder, is one of the leading causes of disability. Chondroitin has emerged as a new treatment. Previous meta-analyses have shown contradictory results on the efficacy of chondroitin. This, in addition to the publication of more trials, necessitates a systematic review.. To evaluate the benefit and harm of oral chondroitin for treating osteoarthritis compared with placebo or a comparator oral medication including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, opioids, and glucosamine or other "herbal" medications.. We searched seven databases up to November 2013, including the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials. We searched the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) websites for adverse effects. Trial registers were not searched.. All randomized or quasi-randomized clinical trials lasting longer than two weeks, studying adults with osteoarthritis in any joint, and comparing chondroitin with placebo, an active control such as NSAIDs, or other "herbal" supplements such as glucosamine.. Two review authors independently performed all title assessments, data extractions, and risk of bias assessments.. Forty-three randomized controlled trials including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control were included. The majority of trials were in knee OA, with few in hip and hand OA. Trial duration varied from 1 month to 3 years. Participants treated with chondroitin achieved statistically significantly and clinically meaningful better pain scores (0-100) in studies less than 6 months than those given placebo with an absolute risk difference of 10% lower (95% confidence interval (CI), 15% to 6% lower; number needed to treat (NNT) = 5 (95% CI, 3 to 8; n = 8 trials) (level of evidence, low; risk of bias, high); but there was high heterogeneity between the trials (T(2) = 0.07; I(2) = 70%, which was not easily explained by differences in risk of bias or study sample size). In studies longer than 6 months, the absolute risk difference for pain was 9% lower (95% CI 18% lower to 0%); n = 6 trials; T(2) = 0.18; I(2) = 83% ), again with low level of evidence.For the Western Ontario and McMaster Universities Osteoarthritis Index Minimal Clinically Important Improvement (WOMAC MCII Pain subscale) outcome, a reduction in knee pain by 20% was achieved by 53/100 in the chondroitin group versus 47/100 in the placebo group, an absolute risk difference of 6% (95% CI 1% to 11%), (RR 1.12, 95% CI 1.01 to 1.24; T(2) = 0.00; I(2) = 0%) (n = 2 trials, 1253 participants; level of evidence, high; risk of bias, low).Differences in Lequesne's index (composite of pain,function and disability) statistically significantly favoured chondroitin as compared with placebo in studies under six months, with an absolute risk difference of 8% lower (95% CI 12% to 5% lower; T(2)= 0.78; n = 7 trials) (level of evidence, moderate; risk of bias, unclear), also clinically meaningful. Loss of minimum joint space width in the chondroitin group was statistically significantly less than in the placebo group, with a relative risk difference of 4.7% less (95% CI 1.6% to 7.8% less; n = 2 trials) (level of evidence, high; risk of bias, low). Chondroitin was associated with statistically significantly lower odds of serious adverse events compared with placebo with Peto odds ratio of 0.40 (95% CI 0.19 to 0.82; n = 6 trials) (level of evidence, moderate). Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug. Adverse events were reported in a limited fashi. A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne's index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Glucosamine; Hand; Humans; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Randomized Controlled Trials as Topic

Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate-a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients.

Topics: Animals; Chemistry, Pharmaceutical; Chondroitin Sulfates; Dietary Supplements; Osteoarthritis; Quality Control

The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA).. Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process.. It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing).. This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA.

Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Europe; Glucocorticoids; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis; Practice Guidelines as Topic; Viscosupplements

Authors reviewed the literature on the efficacy of chondroprotectors in the treatment of chronic pain syndromes in comparison with placebo and other analgesics to discover the own antinociceptive effect of these drugs and mechanisms by which it occurs. Authors evaluated the results of various clinical studies on the effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) on chronic pain syndrome in osteoarthritis and low back pain. We compared their effects with those of NSAIDs, celecoxib, or placebo. Assessment of pain and functional status was performed using WOMAC, VASandLeken's index as well as the Roland--Morrisquality of life questionnaire. The review of a number of clinical studies revealed a definite antinociceptive and anti-inflammatory effect of SYSADOA comparable with NSAIDs not only in the treatment of osteoarthritis, but also in chronic back pain, which is characterized by early onset and gradual development with a long-term retention of the result even after discontinuation of therapy. It has been shown that SYSADOA are able to reduce the level of inflammatory cytokines in the blood (IL-6, C-reactive protein) and to activate the production of anti-inflammatory cytokine IL-10 in the synovial membrane. It is shown that blocking of the effects of interleukin 1-beta and thereby inhibition of inflammatory enzymes like nitric oxide synthase and cyclooxygenase-2 is one of the points of glucosamine chondrocytes application. The data obtained in numerous studies that confirm the ability of SYSADOA to inhibit proinflammatory cytokines open the new perspectives for their use in the treatment of not only joint pain but also other chronic pain syndromes.. Обзор посвящен изучению эффективности назначения хондропротекторов при хронических болевых синдромах в сравнении с плацебо и другими анальгетиками с целью уточнения собственного антиноцицептивного эффекта этих препаратов и механизмов, за счет которых он осуществляется. Была проведена оценка результатов различных клинических исследований по влиянию хондропротекторов на хронический болевой синдром как при остеоартрозе, так и люмбалгии. Изучалось сравнение их эффектов с нестероидными противовоспалительными средствами (НПВС), целекоксибом, плацебо. Оценка болевого синдрома и функционального состояния проводилась по шкалам WOMAC, Лекена и ВАШ, а также по опроснику качества жизни Роланда-Морриса. В ходе обзора ряда клинических исследований выявлен выраженный антиноцицептивный эффект хондропротекторов, сравнимый с таковым у НПВС не только при терапии остеоартроза, но и при хронической боли в спине, характеризующийся ранним началом и постепенным развитием с длительным сохранением результата даже после отмены терапии. Показано, что хондропротекторы способны снижать уровень противовоспалительных цитокинов в крови, таких как интерлейкин-6 (IL-6), С-реактивный белок, и активировать выработку антивоспалительных цитокинов IL-10 в синовиальной мембране. Показано, что одной из точек приложения глюкозамина в хондроцитах является блокирование эффектов интерлейкина-1β, посредством чего также ингибируются воспалительные ферменты, такие как синтаза оксида азота и циклооксигеназа-2. Полученные в многочисленных исследованиях данные, подтверждающие способность хондропротекторов ингибировать провоспалительные цитокины, открывают новые перспективы их применения в терапии не только артралгий, но и других хронических болевых синдромов.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; C-Reactive Protein; Celecoxib; Chondroitin Sulfates; Chronic Pain; Cyclooxygenase 2 Inhibitors; Cytokines; Drug Combinations; Glucosamine; Humans; Interleukin-10; Interleukin-6; Low Back Pain; Nociceptive Pain; Osteoarthritis; Randomized Controlled Trials as Topic; Syndrome

Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOA), such as hyaluronic acid (HA), chondroitin sulfate (CS) and glucosamine (GlcN) are natural compounds, composed of repeating disaccharides, used to treat patients with osteoarthritis (OA). Many questions about the kinetics and mechanism of action of SYSADOA remain poorly answered. This review examines the data supporting oral absorption and body distribution of SYSADOA, and discusses their mechanism of action. SYSADOA are absorbed in the small intestine with a bioavailability ranging from 5 to 45% and accumulate in articular tissues. The mechanism of action of HA and CS differs in several aspects from that of GlcN. Being large molecules, HA and CS do not penetrate into chondrocytes, synoviocytes, osteoblast, osteoclast and osteocytes, and so elicit the anti-inflammatory effect by engaging membrane receptors, e.g. CD44, TLR4, and ICAM1, with a resulting dual effect: impede the fragments of extracellular matrix engaging these receptors, cause of inflammatory reaction, and block the signal transduction pathways activated by the fragments and so diminish the nuclear translocation of pro-inflammatory transcription factors. GlcN penetrates into cells by means of glucose transporters. The primary effect of GlcN is associated to its ability to O-GlcNAcylate proteins and as a consequence, modulates their activity, e.g. decrease nuclear factor-κB nuclear translocation. GlcN may also affect the transcription of pro-inflammatory cytokines by epigenetic mechanisms. The characteristics of the mechanism of action support the use of CS combined with GlcN, and suggest that HA and CS shall be more effective in initial phases of OA.

Topics: Animals; Biological Availability; Chondroitin Sulfates; Glucosamine; Humans; Hyaluronic Acid; Intestinal Absorption; Osteoarthritis; Signal Transduction; Tissue Distribution

Oral supplementation of chondroitin sulphate plus glucosamine helps repair the articular surface in osteoarthritis. Chondroitin-S reduces the concentration of the pro-inflammatory cytokines and transcription factor involved in inflammation. GlcN.S enhances cartilage specific matrix components and prevents collagen degeneration in chondrocytes by inhibiting hydrolytic enzymes, and preventing the oxidation of lipids and proteins. Chondroitin-S plus GlcN.S are slow-acting drugs that alleviate pain and partly restore joint function in OA patients. Orally administered pharmaceutical-grade chondroitin-S plus GlcN.S stabilize the joint space narrowing and significantly decrease the number of patients with new erosive OA. They are safe and no adverse events have ever been reported; they are recommended by EULAR and OARSI. The cost/effectiveness of the oral chondroitin-S plus GlcN.S therapy derives from the reduction of costs for physiotherapy, and for gastroprotective and non-steroidal drugs. The synergistic association of these two world-widely preferred nutraceuticals is a step forward in the management of OA.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Cartilage; Chondrocytes; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis

Condrosulf(®) is a pharmaceutical formulation containing chondroitin sulfate (CS) as an active component possessing high quality and purity and standardized properties. CS is currently applied as a SYSADOA (Symptomatic Slow Acting Drug for Osteoarthritis) agent in Europe in the treatment of osteoarthritis (OA). Furthermore, Condrosulf(®) and pharmaceutical grade CS have also been proven to possess structure-modifying effects belonging to the S/DMOAD (structure/disease modifying anti-osteoarthritis drug) class. This review summarizes current knowledge on CS/Condrosulf(®) structure and its properties, its pharmacological activity as proved by many clinical trials and metaanalysis studies and focuses attention on its mechanisms of action in the pathophysiology of osteoarthritic joint tissues. Finally, future perspectives are discussed in connection with the possibility to apply new outcome measures, such as MRI and biomarkers, which can yield important advances in the use of Condrosulf(®) as well as the development of new drugs with different structures useful in particular for the treatment of inflammatory symptoms and able to retard the progression of arthritis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Humans; Osteoarthritis; Treatment Outcome

With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T(1), T(2) and T(1ρ) relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.

Topics: Animals; Cartilage, Articular; Cattle; Chondroitin Sulfates; Contrast Media; Gadolinium DTPA; Humans; Ligaments; Magnetic Resonance Imaging; Osteoarthritis; Patella; Sheep; Sodium; Tendons

Topics: Chondroitin Sulfates; Drug Combinations; Evidence-Based Medicine; Female; Glucosamine; Hand Joints; Humans; Male; Osteoarthritis; Pain Measurement; Patient Satisfaction; Prognosis; Randomized Controlled Trials as Topic; Range of Motion, Articular; Treatment Outcome

Osteoarthritis is a chronic disease characterized by irreversible damage to joint structures, including loss of articular cartilage, osteophyte formation, alterations in the subchondral bone and synovial inflammation. It has been shown that chondroitin sulfate interferes with the progression of structural changes in joint tissues and is used in the management of patients with osteoarthritis.. This review summarizes data from relevant reports describing the mechanisms of action of chondroitin sulfate that may explain the beneficial effects of the drug and examines the evidence for clinical efficacy of oral chondroitin sulfate in osteoarthritis. Data included in the review were derived from a literature search in PubMed. Literature searches were performed in PubMed using the search terms 'chondroitin sulfate', 'pharmaceutical-grade', 'osteoarthritis', 'randomized clinical trials', 'humans'. The MEDLINE database was searched from January 1996 through August 2012 for all randomized controlled trials, meta-analyses, systematic reviews, and review articles of chondroitin sulfate in osteoarthritis.. Chondroitin sulfate exerts in vitro a beneficial effect on the metabolism of different cell lines: chondrocytes, synoviocytes and cells from subchondral bone, all involved in osteoarthritis. It increases type II collagen and proteoglycan synthesis in human articular chondrocytes and is able to reduce the production of some pro-inflammatory factors and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Clinical trials have reported a beneficial effect of chondroitin sulfate on pain and function. The structure-modifying effects of chondroitin sulfate have been reported and analyzed in recent meta-analyses. The results in knee osteoarthritis demonstrate a small but significant reduction in the rate of decline in joint space width. Because chondroitin sulfate quality of several nutraceuticals has been found to be poor, it is recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements in the treatment of OA. Chondroitin sulfate is recommended by several guidelines from international societies in the management of knee and hip OA. Furthermore, its safety profile is favorable when compared with many other therapies used in OA.. Chondroitin sulfate is an effective and safe treatment option for patients with osteoarthritis.

Topics: Bone and Bones; Cell Line; Chondrocytes; Chondroitin Sulfates; Collagen Type II; Disease Progression; Humans; Inflammation Mediators; Osteoarthritis; Proteoglycans; Synovial Membrane; Treatment Outcome

There is growing evidence of the role that nutrition can play in the management of veterinary patients with osteoarthritis. Current evidence supports nutritional management of body weight and dietary fortification with the long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Additional studies suggest that supplements and diet additives such as glucosamine, chondroitin sulfate, antioxidants, and green-lipped mussel may also have some benefit in managing osteoarthritis. Additional research evaluating pets with naturally occurring disease, using validated owner questionnaires and objective measurements, is needed.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chondroitin Sulfates; Dietary Supplements; Dog Diseases; Dogs; Fatty Acids, Omega-3; Food, Fortified; Glucosamine; Osteoarthritis

According to the European League of Associations of Rheumatology (EULAR) and the American College of Rheumatology (ACR), acetaminophen should be used as a first-line therapy in patients with osteoarthritis, because of its safety and effectiveness. NSAID should be considered in patients unresponsive to acetaminophen, and should be prescribed at the lowest effective dose and for the shortest duration. The use of stronger analgesics, such as weak opioids and narcotic analgesics, is only indicated when other drugs, such as NSAID, have been ineffective or are contraindicated. Symptomatic slow acting drugs (avocado soybean unsaponifiable, chondroitin sulphate, diacerein, glucosamine sulphate) have mild symptomatic effects and may reduce the consumption of NSAID.

Topics: Administration, Oral; Analgesics; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Doxycycline; Humans; Osteoarthritis; Treatment Outcome

Osteoarthritis (ostheoarthrosis, OA) is characterized by progressive destruction of articular cartilage, remodeling of the periarticular bone and inflammation of the synovial membrane. In patients occur joints pain, impaired joints motion and disability. The results of many studies indicate an inflammation as foundation of this disease. The management of OA include a combination of pharmacological treatments and nonpharmacological interventions. Pharmacological treatments include used paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs) and chondroprotectives (glucosamine, chondroitin sulfate and so on). NSAIDs long-term use associated with serious adverse effects. OA symptoms are effectively reduced by nutrients such omega 3 and omega 6 fatty acids (PUFAs as EPA, DHA), which decrease the need for non-steroidal drugs and may less adverse events. They exerts, particularly EPA, anti-inflammatory effect, inhibit catabolic processes, stimulate the anabolic process in the cartilage in the joint. Many different evidence validate that omega 3 alleviate the progression of osteoarthritis and have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory in joints.

Topics: Acetaminophen; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Glucosamine; Humans; Osteoarthritis

Glucosamine and chondroitin sulfate, components of normal cartilage that are marketed as dietary supplements in the United States, have been evaluated for their potential role in the treatment of osteoarthritis. Due to claims of efficacy, increased prevalence of osteoarthritis, and a lack of other effective therapies, there has been substantial interest in using these dietary supplements as therapeutic agents for osteoarthritis. Though pharmacokinetic and bioavailability data are limited, use of these supplements has been evaluated for management of osteoarthritis symptoms and modification of disease progression. Relevant clinical trial efficacy and safety data are reviewed and summarized.

Topics: Analgesics; Animals; Arthralgia; Biological Availability; Cartilage, Articular; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Glucosamine; Humans; Mice; Models, Animal; Osteoarthritis; Rabbits; Treatment Outcome

Dietary supplements have inundated the commercial market in recent times. These so called "health" supplements are being marketed as beneficial in the prevention and regression of several common medical conditions that include osteoarthritis. This review provides an overview of osteoarthritis as a common disease and elucidates the disease process in relation to conventional therapeutic approaches. We also attempt to present perspectives about the dietary industry, focusing on the widely available dietary supplements for osteoarthritis; then we discuss the current available evidence regarding these common dietary supplements which are finally consolidated and enumerated as major key points.

Topics: Chondroitin Sulfates; Dietary Supplements; Drug Industry; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Risk Assessment; Time Factors; Treatment Outcome

The review considers issues of pharmacodynamics and clinical applications of drugs with the metabolic type of action, which stimulate regeneration and provide the protective action on articular cartilage in cases of osteoarthritis. Published data of the experimental and clinical trials of the main chondroprotective agents are analyzed.

Topics: Cartilage, Articular; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Regeneration

Chondroitin sulphate (CS) is recommended by the European League Against Rheumatism as a symptomatic slow-acting drug for the treatment of osteoarthritis on the basis of numerous clinical trials and meta-analyses. Furthermore, recent clinical trials have also demonstrated the possible structure-modifying effects of CS. This review focuses on recent experimental results and data available in the scientific literature regarding the anti-inflammatory properties of CS with a view to understanding the molecular basis responsible for its activity. Several animal studies have demonstrated that orally administered CS significantly inhibited hind paw oedema, synovitis and destruction of the articular cartilage in a dose-dependent manner. Furthermore, CS proved to have a beneficial effect in slowing down the development of adjuvant arthritis and in reducing disease markers, findings which support its beneficial activity in humans as a chondroprotective drug. Finally, several in vitro studies have focused on the hypothesis that CS may reduce inflammatory processes by acting on the nuclear translocation of NF-κB, which is closely associated with the blood biomarkers of inflammation, primarily IL-1, IL-6 and C-reactive protein.

Topics: Animals; Anti-Inflammatory Agents; Chondroitin Sulfates; Clinical Trials as Topic; Humans; Inflammation; Meta-Analysis as Topic; Osteoarthritis

The rheumatic diseases have been associated with accelerated atherosclerosis. Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by persistent synovial inflammation which leads to disability and structural changes in joints. Epidemiological studies have demonstrated an increased cardiovascular mortality in patients with RA. In these patients, atherosclerotic plaque occurs earlier, and it has a faster evolution than in general population. Atherosclerosis (AT) is also an inflammatory disease partly mediated by cytokines, many of them involved on chronic synovitis. Our group has developed a rabbit experimental model of AT aggravated by chronic arthritis to study inflammatory mechanisms involved on the progression of vascular lesions and their response to drugs. A preliminary study using this model suggests a beneficial effect of chondroitin sulphate (CS), a drug recommended for the treatment of osteoarthritis, in controlling AT lesions. Yet clinical trials should be conducted with this compound to address the same hypothesis in human studies.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Atherosclerosis; Chondroitin Sulfates; Humans; Osteoarthritis; Rabbits

Osteoarthritis is a chronic disease characterized by irreversible damage to joint structures, including loss of articular cartilage, inflammation of the synovial membrane, and alterations in the subchondral bone. Symptomatic slow-acting drugs for osteoarthritis have been proposed as treatment because of their excellent safety profile. This review summarizes some data relating to the mechanisms of action of chondroitin sulfate in the pathophysiology of osteoarthritic joint tissues.. Peer-reviewed articles obtained using pre-defined search criteria and published in the PubMed database are summarized. In addition, a relevant in press paper is included.. Chondroitin sulfate belongs to the group of glycosaminoglycans and is a major component of articular cartilage. The effect of chondroitin sulfate in patients with osteoarthritis is possibly the result of the stimulation of the synthesis of proteoglycans and the decrease in catabolic activity of chondrocytes by inhibiting the synthesis of proteolytic enzymes and other factors that contribute to cartilage matrix damage and cause the death of these cells. Chondroitin sulfate was also shown to exert anti-inflammatory activity. In addition, it acts on osteoarthritic subchondral bone osteoblasts by modulating the osteoprotegerin/receptor activator of NF-kappaB ligand ratio in favor of reduced bone resorption. It is noteworthy to mention that a head-to-head comparison of the effects of chondroitin sulfate of different origins and levels of purity on human osteoarthritic cartilage revealed the existence of a disparity in effects.. The positive effects of chondroitin sulfate on the pathophysiology of osteoarthritis are possibly due to its contribution to a proper balance between anabolism/catabolism in the articular tissues.

Topics: Anti-Inflammatory Agents; Bone Remodeling; Cartilage, Articular; Chondroitin Sulfates; Humans; Osteoarthritis; Synovial Membrane

To evaluate the immune-modulator effect of chondroitin sulfate (CS) by means of the review of the literature.. Inflammatory reactions are primarily originated by infectious agents, immune reactions and by sterile tissue lesions that activate membrane receptors by means of pathogen-associated molecular patterns, tissue breakdown products and cytokines. The activation of membrane receptors triggers the phosphorylation of mitogen activated protein kinases and of the nuclear factor kappaB (NF-kappaB). The binding of NF-kappaB to the promoter of target genes enhances the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, phospholipase A2, and matrix metalloproteases, proteins that contribute to tissue damage and to the inflammatory reaction. The activation of NF-kappaB has a key role in the immune homeostasis and the inflammatory response and therefore, in the pathogenesis of numerous diseases. Chondroitin sulfate (CS) is able to diminish NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane, effects that may explain the benefits of CS in osteoarthritis. In addition, systemic CS reduces NF-kappaB nuclear translocation in macrophages and hepatocytes, raising the hypothesis that CS might be of benefit to treat other diseases with a strong inflammatory component. There is preliminary evidence in humans that CS improves moderate to severe psoriasis. Moreover, experimental and clinical data suggest that CS might be a useful therapeutic agent in diseases such as inflammatory bowel diseases, atherosclerosis, Parkinson's and Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis and systemic lupus erythematosus.. These results urge for double blinded placebo-controlled trials to confirm the utility of CS in diseases with immune and inflammatory components.

Topics: Anti-Inflammatory Agents; Atherosclerosis; Chondroitin Sulfates; Humans; Inflammation; Inflammatory Bowel Diseases; Osteoarthritis; Psoriasis

Osteoarthritis (OA) is a common, painful, and debilitating condition that affects approximately 46.4 million individuals in the United States. By 2012, this number is expected to increase to 60 million. In addition, it is the leading cause of activity limitation in adults and represents a widely acknowledged economic burden. Although the ultimate goal is to slow or prevent OA progression, at present, medical management of OA is aimed primarily at controlling symptoms of pain and stiffness and maintaining joint mobility and quality of life. Because of the lack or perceived lack of response to many conventional therapies for OA as well as concerns regarding the long-term administration of drugs (eg, nonsteroidal anti-inflammatory drugs), oral joint health supplements (OJHSs) have become increasingly popular among patients with OA. This article briefly reviews pertinent molecular mechanisms involved in the development of OA and summarizes available in vitro and in vivo evidence supporting the use of avocado and soybean unsaponifiables (ASU) either alone or in combination with glucosamine and chondroitin sulfate in patients with OA. Basic scientific research studies and a systematic review and meta-analysis of the available high-quality randomized clinical trials indicate that 300 mg of ASU per day (with or without glucosamine and chondroitin sulfate) appears to be beneficial for patients with hip or knee OA. There is also some evidence that ASU or ASU/glucosamine/chondroitin sulfate combination products could be used prophylactically in even the earliest stages of OA. Considering concerns regarding inferior-quality OJHSs, consumers and physicians are encouraged to take an evidence-based approach when evaluating OJHSs to identify and recommend safe and effective products that meet label claims when tested independently, and are of the highest quality.

Topics: Chondroitin Sulfates; Dietary Supplements; Glycine max; Humans; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Persea; Quality of Life

Chondroitin sulphate (CS) is widely consumed orally by humans, and non-humans as it is believed to be beneficial for those with joint-related pathologies. Data concerning the functions of chondroitin sulphate in this, and other, biological systems are being actively extended. However, it is important to appreciate that chondroitin sulphate molecules represent a heterogeneous population the structure of which varies with source. As commercially available chondroitin sulphate is derived from a range of sources, and the molecular functions of chondroitin sulphate depend upon the structure, there are a range of structures available with differing potential for therapeutic impacts on a range of pathologies. While the safety of CS is not presently in doubt, poor quality finished products have the potential to compromise clinical and lab-based studies and will fail to give consumers all of the benefits available. Major parameters including bioavailability and uptake have been studied but it is clear that significant challenges remain in the identification of composition, sequence and size impacts on function, understanding how the consumed material is altered during uptake and travels to a site of action and how it exerts an influence on biological processes. If we understand these factors it may be possible to predict impacts upon biological processes and identify specific chondroitin sulphate structures which may target specific pathologies.

Topics: Anti-Allergic Agents; Anti-Inflammatory Agents; Antioxidants; Biological Phenomena; Chondroitin Sulfates; Dietary Supplements; Humans; Joints; Molecular Structure; Osteoarthritis; Urologic Diseases

Osteoarthritis (OA) is the most common arthritis affecting the aging population. This degenerative disease can cause significant pain and functional disability in affected individuals. Despite advances in the retardation of rheumatoid arthritis with disease-modifying agents, comparable oral agents have been relatively unavailable for OA. The mainstays of therapy continue to be acetaminophen and nonsteroidal antiinflammatory medications to manage symptoms. Unfortunately, these medications can precipitate severe adverse events in some patients or may be contraindicated, leaving few choices remaining to control pain and suffering. Glucosamine sulfate and chondroitin sulfate have been evaluated in many studies as agents to relieve pain, improve functional activity, and slow disease progression in OA especially of the hip and knee. Studies have reported conflicting results regarding improvement in the pain and disability associated with OA with the use of glucosamine and chondroitin as single agents; however, when improvement has been demonstrated, the formulation has primarily been glucosamine sulfate combined with chondroitin sulfate. Recently, as a result of information implicating the role of reactive oxygen species and oxidative cellular stress reactions on the onset of neurodegenerative and inflammatory disorders, it has been theorized that medications that could control or alter these reactions might improve or prevent the onset of these conditions. Primorine is a combination of products thought to alter these biochemical oxidative byproducts. Based on current evidence, the use of a combination product of glucosamine sulfate and chondroitin sulfate seems to have the greatest potential as a therapeutic intervention for patients at increased risk from the adverse events of accepted current oral therapies. The use of primorine and its combination of products as an intervention in OA has theoretical advantages but its benefits are unproven. A new product, relamine, is a combination of these three formulations. While no studies have evaluated glucosamine sulfate, chondroitin sulfate and primorine in a single product, it may be an option for those who wish to try an alternate therapy for OA, as there appears to be a low risk for serious adverse events.

Topics: 4-Aminobenzoic Acid; Aged; Chondroitin Sulfates; Clinical Trials as Topic; Drug Combinations; Glucosamine; Humans; Osteoarthritis; Thioctic Acid; Vitamin E

Osteoarthritis (OA) is characterized by increased cartilage degradation and wearing. The principal disease hallmarks for assessment of OA are radiographic aspects. However, laboratory markers of joint fluid, serum or urine have received growing attention in recent years. Biomarkers should be useful for improvement of diagnosis, assessment of disease progression and evaluation of therapeutic effects in OA. Here we described the outline of biomarkers in cartilage including utility and weakness.

Topics: Biomarkers; Cartilage; Chondroitin Sulfates; Collagen Type I; Collagen Type II; Early Diagnosis; Humans; Hyaluronic Acid; Keratan Sulfate; Matrix Metalloproteinases; Osteoarthritis; Peptides; Proteoglycans

Chondroitin sulfate is currently recommended by the European League Against Rheumatism (EULAR) as a SYSADOA (symptomatic slow acting drug for osteoarthritis) in Europe in the treatment of knee and hand osteoarthritis based on research evidence and meta-analysis of numerous clinical studies. Furthermore, recent clinical trials demonstrated its possible structure-modifying effects. Chondroitin sulfate, alone or in combination with glucosamine or other ingredients, is also utilized as a nutraceutical in dietary supplements in Europe and the USA. However, it is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants and many other factors contribute to the overall biological and pharmacological actions of these agents. We aim to review the quality control of chondroitin sulfate in pharmaceutical-grade preparations and nutraceuticals.. Pharmaceutical-grade formulations of chondroitin sulfate are of high and standardized quality, purity and properties, due to the stricter regulations to which this drug is subjected by local national health institutes as regards production and characteristics. On the contrary, as several published studies available in literature indicate, the chondroitin sulfate quality of several nutraceuticals is poor. Additionally, there are no definite regulations governing the origin of the ingredients in these nutraceuticals and the origin of the ingredients in natural products is the most important factor ensuring quality, and thus safety and efficacy, in particular for chondroitin sulfate, due to its extraction from different sources.. Due to the poor chondroitin sulfate quality of some nutraceuticals, we conclude that stricter regulations regarding their quality control should be introduced to guarantee the manufacture of high quality products for nutraceutical utilization and to protect customers from low-quality, ineffective and potentially dangerous products. There is a need for specific and accurate analytical procedures, which should be enforced to confirm purity and label claims both for raw materials and finished chondroitin sulfate products, and also to govern the origin of ingredients. Until these stricter regulations are in place, then it is strongly recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements.

Topics: Animals; Chemistry, Pharmaceutical; Chondroitin Sulfates; Dietary Supplements; Humans; Molecular Structure; Osteoarthritis; Quality Control

Chondroitin sulphate (CS) has attracted much interest over the past two decades or so as a biological agent for use in the relief of pain and joint symptoms in osteoarthritis. Earlier clinical investigations produced variable, if encouraging results. This variability was partly due to limitations on the study designs and the lack of availability of standardized CS. Recently, high quality and fully standardized CS (Condrosulf) has become available and its effects have been studied in large-scale osteoarthritis trials, which are discussed here.. There is now evidence for symptom- and structure-modifying (radiologically-observed) effects. These studies show that CS (a) has slow onset of response and that relief of pain may not be like that of the direct analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs), (b) there are indications of reduced need for intake of analgesics (e.g. NSAIDs) in patients taking CS, and (c) quality of life and cost-benefits may be associated with use of CS. Safety evaluations show that the incidence of adverse reactions is low. Pharmacokinetic studies indicate that although oral absorption is relatively fast CS has moderate oral bioavailability (15-24%) and that depolymerised and degraded CS that is evident after absorption, together with CS itself, may take some time to accumulate in target joints. The pharmacodynamic actions of CS indicate that it has anti-inflammatory effects that include multiple actions involving reduction of catabolic reactions and enhanced anabolic (proteoglycan) synthetic reactions in cartilage and may block osteoclast activation in bone. Further studies are required to (a) establish the effects of depolymerised and degraded CS on degradation of cartilage and bone in vitro, and (b) MRI and other investigations of the effects in osteoarthritis of long-term CS treatment.. The findings from this review show there may be potential value of CS in reducing the dependence on intake of NSAIDs and analgesics in patients with osteoarthritis, while at the same time having favourable safety.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Chondroitin Sulfates; Clinical Trials as Topic; Glycosaminoglycans; Humans; Osteoarthritis

Osteoarthritis is a disabling disease of the aging generation, which results in loss of quality of life and increased healthcare costs. Cytokines appear to play an important role in the cartilaginous degeneration characterizing the pathological process. Increasing experience is being gained with cytokine-modulating therapies aimed at interfering with effects of chondrodegradative cytokines in the synovial fluid. Although in vitro and in vivo effectiveness of several of these therapies has been demonstrated, clinical effectiveness remains disputable, which may be related to the low levels of inflammatory cytokines found in osteoarthritic joints. By contrast, directly after joint trauma, which has been shown to predispose to early osteoarthritis, synovial fluid cytokine levels are strongly increased. Cytokine-modulating therapies, however, have hardly been considered for this indication. Increased knowledge of intra-articular soluble mediators correlating with cartilage pathology will lead to further development of cytokine-modulating products and, eventually, to effective inhibition of cartilage degeneration, in both the osteoarthritic as well as injured joints.

Topics: Animals; Cartilage; Chondroitin Sulfates; Cytokines; Humans; Immunotherapy; Inflammation; Knee Injuries; Knee Joint; Osteoarthritis; Risk Factors; Synovial Fluid

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability in the United States, especially among older adults. Treatment options have primarily focused on alleviating the pain often associated with this condition. Acetaminophen and nonsteroidal anti inflammatory drugs (NSAIDs) are often employed for relief of mild-to moderate pain associated with OA. NSAIDs are typically more effective than acetaminophen; however, because of adverse effects associated with long-term use of NSAIDS, acetaminophen is considered first-line therapy. Safety concerns of traditional pharmacotherapeutic agents used in the management of OA, such as NSAIDs and opioids, have led healthcare professionals to seek other options. Trials of disease modulating agents that focus on preventing further damage to the joints have the potential to change how this disease state is managed. This article reviews nonpharmacologic and pharmacologic approaches to management of OA of the knee and hip.

Topics: Acetaminophen; Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Pain; Patient Education as Topic; Risk Factors; United States

Chondroitin sulfate (CS) is an omnipresent glycosaminoglycan with significant biologic roles. Chondroitin sulfate has not one structure but its polysaccharide backbone is modified to a smaller or higher degree according to the cell, tissue, species localization, and/or physiopathological stimuli. The potential of chondroitin sulfate for the therapy of osteoarthritis has been under investigation in several clinical trials, which have shown that it is safe and well tolerated. However, there are many issues still unresolved, such as the structure-modifying effects of CS in osteoarthritis, symptom-modifying efficacy in certain groups of patients, structure-activity-pharmacokinetic relationships, knowledge of mechanism of action, and better quality control of the preparations. Furthermore, ongoing basic research on its biologic role will probably show other therapeutic applications.

Topics: Animals; Chondroitin Sulfates; Clinical Trials as Topic; Humans; Osteoarthritis

Symptomatic slow-acting drugs for the treatment of osteoarthritis (SYSADOA; OA) are compounds which are prescribed as drugs in European countries since many years, whereas they are sold as nutraceuticals in USA. In Europe, the publication of the EULAR Recommendations for the Treatment of Knee OA in 2003 has listed oral chondroitin sulfate (CS) as evidence 1A and strength of recommendation A which represents the highest level for a therapeutic strategy. Symptomatic slow-acting drugs are intended to be used as ground therapy for OA; these compounds are not rapidly acting agents such as Non Steroidal Anti-Inflammatory Drugs (NSAIDs), and their clinical efficacy on algo-functional symptoms can only be demonstrated after a couple of weeks of regular intake. Interestingly, once the administration is stopped, they do show carry-over effects of various durations, from about 3 months with the oral formulations to 6-9 months with intra-articular formulations. The main rationale behind the use of the SYSADOA therapeutic class is the reduction of NSAIDs in the overall drug management of OA disease and therefore consequently to limit the very significant risks of upper Gastro-intestinal (GI) tract erosions, ulcers with bleeding and/or deleterious renal effects in elderly patients. The evidence for clinical efficacy of oral CS as a drug able to significantly improve the algo-functional symptoms of OA disease does come from a set of randomized clinical studies published a couple of years ago. Indeed, it was demonstrated that the drug was effective in knee and finger OA, whereas previous data suggested that hip OA patients could also benefit from it. In addition, oral CS supported the comparison with NSAIDs such as diclofenac sodium in a medium/long-term clinical study in patients with knee OA. A dose-finding study in patients with knee OA did provide strong data supporting the administration of 800 mg of CS orally which had nearly the same effects as 1200 mg/day, whereas the use of a sequential 3 months administration mode, twice a year was also shown to provide the same results as a continuous treatment. The good tolerability and safety aspects of oral CS were largely documented in these CTs. Taking these important points into account, we definitively have enough clinical data available supporting the view that oral CS is a valuable and safe symptomatic treatment for OA disease. More recent data based on a couple of previous trials and two pivotal studies do provide fu

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Finger Joint; Humans; Knee Joint; Meta-Analysis as Topic; Osteoarthritis; Radiography; Randomized Controlled Trials as Topic; Treatment Outcome

This article describes what structure modification is, explains the distinctions among preventing, retarding, stopping, and reversing disease, and suggests approaches that might be clinically meaningful. It discusses whether any evidence suggests it is possible to modify disease and whether the current focus on cartilage is appropriate. It considers the methodologic approaches and the obstacles to demonstrating efficacy of these agents in clinical trials. The authors hope that at the end of this narrative review the reader will appreciate the complexities of this rapidly evolving field and of the development of disease-modifying drugs for osteoarthritis drugs.

Topics: Adjuvants, Immunologic; Aged; Cartilage, Articular; Chondroitin Sulfates; Doxycycline; Drug Delivery Systems; Female; Forecasting; Glucosamine; Hip Joint; Humans; Hyaluronic Acid; Knee Joint; Male; Middle Aged; Osteoarthritis; Protective Agents; Risk Factors; Synovial Membrane; Treatment Outcome

Glucosamine and chondroitin sulfate are the most well-marketed dietary supplements directed toward managing symptoms associated with osteoarthritis. The presumption of their benefit in the ankle is based largely on promising results from their use in knee osteoarthritis. Likewise, viscosupplementation has proved to be efficacious in the management of osteoarthritis of the knee. Preliminary studies demonstrate a realization of this benefit in the ankle joint, but further research is required. So far, the literature has shown the dietary and viscosupplementation discussed in this article to be relatively safe for use.

Topics: Ankle Joint; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Hyaluronic Acid; Osteoarthritis; Viscosupplementation

There is an increasing incidence in osteoarthritis, particularly following the 5th life-decade. However, also young people may suffer from severe osteoarthritis, which is estimated to be the most common cause of disability in adults resulting in substantial economic burden. To this end, effective therapies are needed. Therapeutic options are very comprehensive, which are presented in this review as non-pharmacological, pharmacological and surgical treatment modalities. Treatment efficacy will be discussed with regard to alleviation of symptoms and potential prevention of disease progression according to the given evidence.

Topics: Administration, Oral; Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Combined Modality Therapy; Complementary Therapies; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Joint Prosthesis; Osteoarthritis; Treatment Outcome

Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Chondroitin Sulfates; Dermatan Sulfate; Drug Discovery; Glycosaminoglycans; Humans; Infections; Liver Regeneration; Neoplasms; Neurodegenerative Diseases; Osteoarthritis

Symptomatic slow-acting drugs (SYSADOA) have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA).. The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations.. Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed.. In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

Topics: Anthraquinones; Antirheumatic Agents; Calcitonin; Chondroitin Sulfates; Clinical Trials as Topic; Etidronic Acid; Glucosamine; Humans; Hyaluronic Acid; Organometallic Compounds; Osteoarthritis; Outcome Assessment, Health Care; Plant Extracts; Risedronic Acid; Thiophenes

Osteoarthritis is a chronic disease characterised by irreversible damage to joint structures, including loss of articular cartilage, osteophyte formation, alterations in the subchondral bone and synovial inflammation. Pain, functional disability and impairment of health-related quality of life are major complaints in patients with osteoarthritis. Several compounds have been investigated for their positive effects on the relief of clinical symptoms and improvement of structural changes in osteoarthritis. It has been shown that chondroitin sulphate interferes with the progression of structural changes in joint tissues and is used in the management of patients with osteoarthritis. This review summarises data from relevant reports describing the mechanisms of action of chondroitin sulphate involved in the beneficial effects of the drug.

Topics: Anti-Inflammatory Agents; Apoptosis; Biological Availability; Bone and Bones; Cartilage, Articular; Chondroitin Sulfates; Humans; Osteoarthritis; Protease Inhibitors; Proteoglycans

A large number of dietary supplements are promoted to patients with osteoarthritis and as many as one third of those patients have used a supplement to treat their condition. Glucosamine-containing supplements are among the most commonly used products for osteoarthritis. Although the evidence is not entirely consistent, most research suggests that glucosamine sulfate can improve symptoms of pain related to osteoarthritis, as well as slow disease progression in patients with osteoarthritis of the knee. Chondroitin sulfate also appears to reduce osteoarthritis symptoms and is often combined with glucosamine, but there is no reliable evidence that the combination is more effective than either agent alone. S-adenosylmethionine may reduce pain but high costs and product quality issues limit its use. Several other supplements are promoted for treating osteoarthritis, such as methylsulfonylmethane, Harpagophytum procumbens (devil's claw), Curcuma longa (turmeric), and Zingiber officinale (ginger), but there is insufficient reliable evidence regarding long-term safety or effectiveness.

Topics: Anti-Inflammatory Agents; Chondroitin Sulfates; Curcuma; Dietary Supplements; Dimethyl Sulfoxide; Glucosamine; Harpagophytum; Humans; Osteoarthritis; Phytotherapy; Plant Preparations; S-Adenosylmethionine; Sulfones; Treatment Outcome; Zingiber officinale

Topics: Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Glucosamine; Hyaluronic Acid; Joints; Osteoarthritis; Treatment Outcome

Chondroitin sulphate (CS) is an important structural component of cartilage and is approved and regulated as a symptomatic slow-acting drug for osteoarthritis (OA) (SYSADOA) in Europe and some other countries. Although numerous studies have shown the clinical benefits of CS to decrease pain, improve functional disability, reduce non-steroidal anti-inflammatory drug (NSAID) or acetaminophen consumption, and good tolerability with an additional carry-over effect, there are still some concerns regarding its effectiveness in treating OA.. To examine the data provided by meta-analyses to clarify the effectiveness of CS as a symptomatic treatment for OA.. A MEDLINE database search was conducted for appropriate meta-analyses published between 1997 and 2007. Five meta-analyses that limited their analysis to randomised controlled trials (RCTs) comparing CS with placebo or no-treatment control arms were retrieved.. Four meta-analyses showed significant clinical effects of CS compared with placebo for pain and function measures and one demonstrated greater reduction of analgesic co-medication in patients assigned to the active treatment. In one meta-analysis, the 20 trials included in the study showed a high degree of heterogeneity and the conclusion that CS showed minimal symptomatic benefits was based on the analysis of only three trials. One meta-analysis showed that pain relief after CS treatment steadily increased between 4 and 12 weeks of treatment, whereas the time course of pain relief after treatment with NSAIDs decreased. Two meta-analyses reported consistently higher frequencies of side effects in the placebo group than in patients treated with CS.. Data provided by these meta-analyses indicate that CS has a slight to moderate efficacy in the symptomatic treatment of OA, with an excellent safety profile.

Topics: Aged; Chondroitin Sulfates; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Meta-Analysis as Topic; Middle Aged; Osteoarthritis; Pain Measurement; Prognosis; Randomized Controlled Trials as Topic; Range of Motion, Articular; Recovery of Function; Severity of Illness Index; Treatment Outcome

Osteoarthritis (OA) treatment is limited by the inability of prescribed medications to alter disease outcome. As a result, patients with OA often take food substances called nutraceuticals in an attempt to affect the structural changes that occur within a degenerating joint. The role of nutraceuticals in OA management can be defined only by an evidence-based approach to support their use. This paper reviews the clinical trials studying glucosamine, chondroitin sulfate, vitamin C, vitamin E, and avocado-soybean unsaponifiables. It highlights the need for additional randomized, placebo-controlled trials to further define the utility of nutraceuticals in OA treatment.

Topics: Ascorbic Acid; Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Glycine max; Humans; Osteoarthritis; Persea; Plant Extracts; Randomized Controlled Trials as Topic; Vitamin E

Chondroitin sulfate is a very heterogeneous polysaccharide in terms of relative molecular mass, charge density, chemical properties, biological and pharmacological activities. It is actually recommended by EULAR as a symptomatic slow acting drug (SYSADOA) in Europe in the treatment of knee osteoarthritis based on meta-analysis of numerous clinical studies. Chondroitin sulfate is also utilized as a nutraceutical in dietary supplements mainly in the United States. On the other hand, chondroitin sulfate is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants, and many other factors contribute to the overall biological and pharmacological actions of these agents. The aim of this review is to evaluate new possible more specific analytical approaches to the determination of the origin and purity of chondroitin sulfate preparations for pharmaceutical application and in nutraceuticals, such as the evaluation of the molecular mass values, the constituent disaccharides, and the specific and sensitive agarose-gel electrophoresis technique. Furthermore, a critical evaluation is presented, together with a discussion of the limits of these analytical approaches. Finally, the necessity for reference standards having high specificity, purity and well-known physico-chemical properties useful for accurate and reproducible quantitative analyses will be discussed.

Topics: Animals; Cartilage; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Dietary Supplements; Disaccharides; Drug Contamination; Electrophoresis, Agar Gel; Glycosaminoglycans; Humans; Molecular Structure; Molecular Weight; Osteoarthritis; Quality Control; Reference Standards; Reproducibility of Results; Technology, Pharmaceutical

Chondroitin sulfate (CS) is a complex carbohydrate polymer with variable sulfation which impacts function. CS exhibits a wide range of biological activities. Many experimental and clinical data are available, affirming that CS represents an effective and safe symptomatic treatment of osteoarthritis (OA) with delayed and sustained effects.

Topics: Animals; Chondroitin Sulfates; Clinical Trials as Topic; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Conformation; Osteoarthritis

Topics: Administration, Oral; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Evidence-Based Medicine; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Meta-Analysis as Topic; Osteoarthritis

The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.

Topics: Aggrecans; Alleles; Cartilage, Articular; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; DNA; Electrophoresis, Agar Gel; Extracellular Matrix Proteins; Gene Expression Regulation; Humans; Hyaluronic Acid; Intervertebral Disc; Lectins, C-Type; Osteoarthritis; Polymerase Chain Reaction; Polymorphism, Genetic; Protein Structure, Tertiary; Spinal Diseases

Recent glycobiology studies have suggested fundamental biological functions for chondroitin sulfate (CS) and dermatan sulfate (DS), which are widely distributed as glycosaminoglycans (GAGs) sidechains of proteoglycans (PGs) in the extracellular matrix and at cellular level. Several biological functions are closely associated with the structure and in particular with the sulfation patterns of these polysaccharides. CS is also used as a structure-modifying osteoarthritis (OA) drug that reverses, retards, or stabilizes the pathology of OA, thereby providing symptomatic relief in the long-term treatment. Advances in analytical separational techniques, including agarose-gel electrophoresis, high-performance liquid chromatography (HPLC), capillary electrophoresis (HPCE), fluorophore-assisted carbohydrate electrophoresis (FACE) and electrospray ionization mass (ESI-MS) enable us to examine alterations of CS/DS with respect to their quantities and fine structural features in various pathological conditions, thus becoming applicable for diagnosis. Furthermore, sensitive analytical procedures enable us to follow the pharmacological application of CS in the treatment of OA and to monitor the progression of the disorder. In this review, the chromatographic and electromigration procedures developed to analyse and characterise CS/DS are presented. Moreover, a critical evaluation of the biological relevance of the results obtained by the developed methodology is discussed.

Topics: Animals; Carbohydrates; Chondroitin Sulfates; Chromatography, Gas; Chromatography, High Pressure Liquid; Connective Tissue; Connective Tissue Diseases; Electrophoresis, Agar Gel; Humans; Osteoarthritis; Spectrometry, Mass, Electrospray Ionization

Dietary supplements and single joint treatments are gaining increasing popularity, with evidence of efficacy in randomized controlled trials compared with placebo, and minimal side-effects compared with some more traditional therapies. This article clarifies some of the newer approaches and the science behind them.

Topics: Adrenal Cortex Hormones; Chondroitin Sulfates; Dietary Supplements; Fish Oils; Glucosamine; Humans; Injections, Intra-Articular; Minerals; Osteoarthritis; Phytotherapy; Vitamins

Complementary or alternative therapies for osteoarthritis are commonly used and therefore it is important that health-care providers and patients are aware of the evidence for or against these approaches. In this article, the best available evidence is reviewed. The results suggest that, for several treatments, the risk-benefit profile is encouraging: acupuncture, several herbal medicines and capsaicin cream. For other therapies the evidence is weak or contradictory: homeopathy, magnet therapy, tai chi, leech therapy, music therapy, yoga, imagery and therapeutic touch. Many other treatments have not been scientifically tested. It is concluded that some complementary or alternative therapies have generated sufficiently promising results to warrant further investigation in large-scale, definitive, randomized clinical trials.

Topics: Acupuncture Therapy; Chondroitin Sulfates; Complementary Therapies; Glucosamine; Homeopathy; Humans; Magnetics; Osteoarthritis; Phytotherapy; Tai Ji; Yoga

The term "symptomatic slow-acting drugs for osteoarthritis" (SySADOA) was coined more than a decade ago to designate medications and/or nutritional supplements used to alleviate the manifestations of osteoarthritis in the long-term. Their efficacy has always been a focus of considerable skepticism. However, a critical reappraisal of the available data, which include results of carefully designed clinical trials conducted in accordance with Good Clinical Practice guidelines, strongly suggests a therapeutic effect. The effects of SySADOA need to be determined based, in particular, on treatment objectives (symptom relief, decreased use of nonsteroidal antiinflammatory drugs and other conventional agents, decreased radiographic progression, and decreased use of joint replacement surgery). In addition, the characteristics of the patients who are most likely to benefit from SySADOA need to be identified.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Humans; Osteoarthritis; Treatment Outcome

Topics: Animals; Blood Coagulation; Cartilage; Chondroitin Lyases; Chondroitin Sulfates; Dermatan Sulfate; Humans; Neoplasms; Osteoarthritis; Polysaccharides; Signal Transduction

Topics: Animals; Chondrocytes; Chondroitin Sulfates; Humans; Neurons; Osteoarthritis; Transforming Growth Factor beta

Topics: Animals; Chondrocytes; Chondroitin Sulfates; Humans; In Vitro Techniques; Interleukin-1beta; NF-kappa B; Osteoarthritis

Topics: Chondrocytes; Chondroitin Sulfates; Finger Joint; Humans; Interleukin-1; Knee Joint; Osteoarthritis; Randomized Controlled Trials as Topic

Topics: Chondrocytes; Chondroitin Sulfates; Connective Tissue; Finger Joint; Humans; Osteoarthritis; Tumor Necrosis Factor-alpha

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Clinical Trials as Topic; Drug Therapy, Combination; Glucosamine; Horse Diseases; Horses; Humans; Osteoarthritis; Treatment Outcome

Therapy of osteoarthritis requires a combination of pharmacological and non-pharmacological modalities. Management should be individualized according to the constitutional features of the patient, comorbidities, disease status, treatment availability and costs. Paracetamol is the analgesic of choice. Beside NSAIDs and intra-articular steroids, SYSADOA have symptomatic effects and may modify structure. Patient education, exercises, orthopaedic devices and physical therapy are indicated as supportive therapy. Alternative therapy modalities should be discussed with the patient using the available evidence and the cost/benefit ratio.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Chondroitin Sulfates; Exercise Therapy; Humans; Osteoarthritis; Palliative Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Severity of Illness Index; Steroids; Treatment Outcome

There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti-inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused.

Topics: Amino Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bivalvia; Camellia sinensis; Cartilage; Chondroitin Sulfates; Fatty Acids, Essential; Flavonoids; Glucosamine; Glucose; Humans; Nutritional Status; Obesity; Osteoarthritis; Osteochondritis Dissecans; Phenols; Polyphenols; Trace Elements; Vitamins

This review summarizes recent knowledge on the efficacy of glucosamine (GS) and/or chondroitin sulfate (CS) in the therapy of mild to moderate osteoarthritis (OA). OA, the most common joint disease is a significant source of disability, quality of life impairment and a considerable burden to any health care system. In the Czech Republic, glucosamine sulfate (GS) and chondroitin sulfate (CS) are available both as prescription drugs and as food supplements. Based on available data both are useful in the earlier stages of OA when combined with other modalities such as weight loss and exercises. They appear to relieve pain and improve range of the joint motion. In addition, they also display mild anti-inflammatory effects. However, controversy still exists over their ability to change significantly the natural history of the osteoarthritic joint. This effect is not easy to demonstrate for any other treatment modalities apart from joint replacement. Monitoring the cure efficacy by X-ray has been recently criticised and hence future techniques are anticipated for this reason. Further, long-term oral administration is required to obtain slightly increased levels of GS and/or CS in human blood. Both reviewed saccharides are well tolerated with negligible adverse reactions. In conclusion, the authors suggest that GS and CS should be classified as food supplements only.

Topics: Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

In horses, lameness is often attributable to some degree of osteoarthritis (OA), a complex disease process that is highlighted by eventual degradation of articular cartilage. Conventional therapies for OA in horses are designed to relieve pain and discomfort and often include pharmacologic intervention with nonsteroidal anti-inflammatory drugs or intra-articular steroids. Oral administration of nutraceutical products to the horse is common and easy and is perceived to be a benign treatment for OA in horses. The main goal for use of nutraceuticals is to use them in OA cases to attempt to lower the dose of other drugs that are more problematic while potentially preventing further degradation (disease or structure modifying). This article attempts to define a nutraceutical, identifies areas that need to be considered when these products are used, and describes the known scientific effects of the most common compounds contained in currently available equine nutraceuticals.

Topics: Animals; Anti-Inflammatory Agents; Cartilage, Articular; Chondroitin Sulfates; Complementary Therapies; Drug Therapy, Combination; Glucosamine; Horse Diseases; Horses; Lameness, Animal; Osteoarthritis; Phytotherapy; Safety; Treatment Outcome

The use of drugs for the treatment of osteoarthritis, with a view to obtain a long-term symptomatic as well as structural benefit, is still in a preliminary state. Nowadays, matricial precursors, such as glucosamine sulfate, are an interesting approach in this indication. They have demonstrated a symptomatic efficacy comparable to that of N.S.A.I.D., with significantly reduced side-effects. Glucosamine sulfate also appears to positively interfere with the structural evolution of osteoarthritis by preventing joint space narrowing which characterizes the evolution of the disease. Encouraging results have also been obtained with chondroitin sulfate and diacerein. As for other molecules, new studies should be undertaken to confirm the results already obtained.

Topics: Anthraquinones; Chondrocytes; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Plant Extracts

Structure-modifying osteoarthritis (OA) drugs are agents that reverse, retard, or stabilize the pathology of OA, thereby providing symptomatic relief in the long-term treatment. The objective of this review is to evaluate the literature on chondroitin sulfate (CS) with respect to the pathobiology of OA to ascertain whether this agent should be classified as a symptomatic slow-acting drug (SYSADOA), a compound that has a slow onset of action and improve OA symptoms after a couple of weeks. CS exhibits a wide range of biological activities and from a pharmacological point of view it produces a slow but gradual decrease of the clinical symptoms of OA and these benefits last for a long period after the end of treatment. Many literature data show that CS could have an anti-inflammatory activity and a chondroprotective action by modifying the structure of cartilage. These properties are also related to the oral adsorption of this molecule as high-molecular mass compounds having clusters of sulfate groups and high charge density capable of exert their chondroprotective activity in vivo.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Clinical Trials as Topic; Humans; Osteoarthritis

Americans spend more on natural remedies for osteoarthritis than for any other medical condition. In treating osteoarthritis, glucosamine and chondroitin sulfate, two of the molecular building blocks found in articular cartilage, are the most commonly used alternative supplements. In randomized trials of variable quality, these compounds show efficacy in reducing symptoms, but neither has been shown to arrest progression of the disease or regenerate damaged cartilage. Although few clinical trials on S-adenosylmethionine exist, preliminary evidence indicates that it relieves pain to a degree similar to that of nonsteroidal anti-inflammatory drugs but with fewer side effects. Clinical trials of dimethyl sulfoxide offer conflicting results. Neither ginger nor cetyl myristoleate has proven clinical usefulness.

Topics: Chondroitin Sulfates; Complementary Therapies; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis; S-Adenosylmethionine

Topics: Cartilage, Articular; Chondroitin Sulfates; Disease Progression; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Regeneration; Treatment Outcome

The use of glucosamine and chondroitin sulfate for the symptomatic treatment of osteoarthritis has been a subject of controversy for several reasons. First, the medical community in general took offense at the title of Theodosakis' book, The Arthritis Cure. Second, the medical community is becoming divided into "traditional" and "alternative" camps with deep skepticism between them. Third, the whole nutraceutical industry is essentially unregulated, with manufacturers making outrageous claims on products that have never been tested at all, are often of poor quality, and occasionally lacking in any active ingredient. However, for the nutriceuticals evaluated here, there is abundant in vitro, in vivo, animal clinical, and human clinical evidence of both their efficacy and safety. They deserve a prominent place in the armamentarium of nonsurgical treatment of osteoarthritis.

Topics: Animals; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis (OA). The most compelling evidence of a potential for inhibiting the structural progression of OA has been obtained with glucosamine sulfate, while some preliminary results also suggest that other compounds could be used in the same indication. At any rate, several medications have clearly demonstrated a symptomatic action, mainly in OA of the lower limbs, including pain relief and improvement of functional disability. An important issue is that all conclusive studies with such chemical entities resulted from the use of prescription medicines and not over-the-counter or nutriceutical supplements.

Topics: Anthraquinones; Anti-Inflammatory Agents; Chondroitin Sulfates; Glucosamine; Humans; Nonprescription Drugs; Osteoarthritis; Plant Oils

Several entities have been investigated carefully for the symptomatic and structural management of osteoarthritis. This review reports recent findings suggesting that such compounds may delay the structural progression of osteoarthritis.. The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, whereas preliminary results obtained in patients with osteoarthritis of the hands also suggest that chondroitin sulfate could be used in the same indication. At any rate, these two compounds have clearly demonstrated a symptomatic action, mainly in osteoarthritis of the lower limbs. Patients with the less severe radiographic osteoarthritis will experience, in the long run, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs.. Glucosamine sulfate has demonstrated its ability to reduce the progression of osteoarthritis in the lower limbs. The preliminary results obtained in the hands suggest that chondroitin sulfate could also be of interest in this indication. An important issue is that all the conclusive studies with such chemical entities resulted from the use of prescription medicines, not over-the-counter pills or food supplements.

Topics: Antirheumatic Agents; Chondroitin Sulfates; Disease Progression; Glucosamine; Humans; Osteoarthritis

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Drug Therapy, Combination; Exercise; Glucosamine; Humans; Injections, Intra-Articular; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteotomy; Physical Therapy Modalities

ARTHROSIS TODAY: Representing the most frequent articular pathology, the prevalence of which increases with age, arthrosis associates elements of construction and destruction. It is a disease of the cartilage in which genetic, mircotraumas, cytokines and microcrystals intervene, associated with abnormalities (notably alteration in density) of the sub-chondral bone. From a therapeutic point of view, the surgical, medicinal or non-pharmacological treatments that are currently available are of unconfirmed efficacy for some of them. CLINICAL-RADIOLOGICAL PARAMETERS AND BIOCHEMICAL MARKERS: A comparison of the levels of biochemical markers with radiological progress and the algofunctional indices in patients presenting with gonarthrosis has shown that, although there is no clear parallel, there are however certain correlations. The chondroïtin sulfates ACS4-ACS6 may intervene not only in radiological progression but also in articular metabolism.. Several local and systemic biomechanical factors (notably anklyzing hyperostosis) are significantly related to gonarthrosis, whereas tobacco abuse has a protective role. Compensated soles and internal femorotibial athrosis of the knee A prospective study conducted over 2 years did not show any symptomatic or structural effect of wearing compensated soles in internal gonarthrosis. However the consummation of non-steroid anti-inflammatories was reduced and compliance was improved. Following prosthesis of the hip the quality of life of patients having been operated on was similar to that of the control group. However, in nearly one third of the patients, there was no significant improvement in pain and/or articular function. Old age, severe pre-surgical pain, and concomitant muscle-skeleton affections represent factors that are of poor post-surgery prognosis.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Biomarkers; Biomechanical Phenomena; Chondroitin Sulfates; Diagnosis, Differential; Double-Blind Method; Female; Humans; Longitudinal Studies; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Odds Ratio; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors; Shoes; Surveys and Questionnaires

THE MECHANISMS OF ACTION ALREADY KNOWN: In vitro, chondroïtin sulfate ACS4-ACS6 have a dose-dependent inhibiting effect on the catabolism of proteoglycanes and collagen. They also stimulate the synthesis of extracellular matrix macromolecules. The existence of a chondrocyte cyto-protector effect and a potentially chondro-protective effect has also been demonstrated. ANOTHER MECHANISM OF ACTION: A new regulation route of chondrocyte metabolism has been proposed in which the Insulin Growth Factor (IGF-1) impedes the catabolic effects of another cytokine, Interleukin 1 (IL-1), by increasing its antagonistic receptor. This control appears essential in the maintenance extracellular matrix homeostasis. CARTILAGE WITH OSTEOARTHRITIS: Chondrocytes from OA cartilage have the capacity to produce more constituting macromolecules of the extracellular matrix. Conversely, these same cells have a greater catabolic capacity. The enhanced activity of IL-1 and the concomitant decrease in its antagonistic receptors leads to the reduction in macromolecule levels in the extracellular matrix, produced in the Cell-associated matrix of OA chondrocytes. ANTI-CATABOLIC EFFECT: It has been demonstrated that ACS4-ACS6 are capable of neutralizing the enhanced catabolic capacity of activated human OA chondrocytes.

Topics: Animals; Cartilage, Articular; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Collagen; Collagen Type II; Extracellular Matrix; Fibronectins; Flow Cytometry; Homeostasis; Humans; Insulin-Like Growth Factor I; Interleukin-1; Osteoarthritis; Osteoarthritis, Knee; Rabbits; Time Factors

The nutritional supplements glucosamine and chondroitine sulphate are widely used in the treatment of osteoarthritis. In published studies, glucosamine used in a dosage of 1.5 gram daily is, after a period of 2 to 4 weeks, just as effective as low doses of NSAIDs in alleviating pain. Chondroitine sulphate has been less well investigated. There are indications that it affects the symptoms of osteoarthritis, even though this effect only occurs after a longer period of time. The side effects for both substances are minor. A disease-modifying effect (defined as delay of radiological progression of osteoarthritis) has not been proven.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

Osteoarthritis affects more patients than almost any other musculoskeletal disorder. The number of patients suffering joint pain and stiffness as a result of this disease will increase rapidly in the next decade. Although operative treatments of patients with osteoarthritis will continue to improve and the number of operative procedures will increase slightly in the next decade, only a small fraction of the patients with osteoarthritis will require operative procedures. The most pressing healthcare need for the majority of patients with osteoarthritis is nonoperative care that helps relieve symptoms and improve function, and in some instances slows progression. In rare instances, the symptoms of osteoarthritis improve spontaneously, but most patients need nonoperative care for decades. Orthopaedists need to improve their ability to provide nonoperative care for patients with osteoarthritis. They should be skilled in the early diagnosis of osteoarthritis and in the use of current common nonoperative treatments including patient education, activity modification, shoe modifications, braces, oral analgesics, oral nonsteroidal antiinflammatory medications, oral dietary supplements, and intraarticular injections. Furthermore, orthopaedists should be prepared to incorporate new nonoperative treatments for patients with osteoarthritis into their practice.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Exercise; Glucosamine; Humans; Hyaluronic Acid; Orthotic Devices; Osteoarthritis; Osteoarthritis, Knee

Topics: Chondroitin Sulfates; Diclofenac; Half-Life; Humans; Osteoarthritis; Predictive Value of Tests; Statistics as Topic; Time Factors

Topics: Cartilage, Articular; Chondroitin Sulfates; Clinical Trials as Topic; Hip Joint; Humans; Knee Joint; Osteoarthritis; Pain Measurement

To examine the efficacy of chondroitin sulfate (CS) in the treatment of osteoarthritis (OA) on the basis of a metaanalysis of controlled clinical trials.. After personal, Medline, and Embase searches, a decision tree analysis of the available publications was performed, with respect to types of joint involvement studied, study designs, numbers of patients enrolled, and variables analyzed. The Lequesne index and pain rating on visual analog scale (VAS) were considered the main variables. Of a total of 16 publications found, 7 trials of 372 patients taking CS could be enrolled into the metaanalysis. Although all selected studies claimed to be randomized, double blind designs in parallel groups, it should be noted that CS was given along with analgesics or nonsteroidal antiiflammatory drugs, making required dosage of comedication an important factor.. Following patients to 120 or more days, CS was shown to be significantly superior to placebo with respect to the Lequesne index and pain VAS. Pooled data confirmed these results and showed at least 50% improvement in the study variables in the CS group compared to placebo.. CS may be useful in OA, but further investigations in larger cohorts of patients for longer time periods are needed to prove its usefulness as a symptom modifying drug in OA.

Topics: Chondroitin Sulfates; Humans; Osteoarthritis; Randomized Controlled Trials as Topic

Topics: Animals; Chondroitin Sulfates; Clinical Trials as Topic; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

Two potentially chondro-protective substances are compared with each other: polymeric chondroitin sulfate and monomeric glucosamine. Chondroitin-sulfate is characterized by tropism for cartilage, i.e. it is preferentially incorporated into cartilagenous tissue. This quality could be of interest in the SPECT-analysis of osteoarthritic knee joints. In contrast to the classic agents Ibuprofen and Indomethacin, the antiinflammatory action of chondroitin-sulfate is less prominent, but the drug does not show any toxic side effects. Glucosamine on the other hand is a multifunctional precursor of the glycosaminoglycan synthesis in general. It lacks the cartilage tropism of chondroitin-sulfate. Into what sort of a glycosaminoglycan glucosamine is eventually integrated, depends therefore on the nature of the cells participating in the biosynthesis.

Topics: Aggrecans; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Extracellular Matrix Proteins; Glucosamine; Humans; Lectins, C-Type; Menisci, Tibial; Osteoarthritis; Proteoglycans; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Synovial Fluid; Tomography, Emission-Computed, Single-Photon

Topics: Chondroitin Sulfates; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome

Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis. The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, while some preliminary results also suggest that chondroitin sulfate could be used in the same indication. At any rate, these two compounds have clearly demonstrated a symptomatic action, mainly in osteoarthritis of the lower limbs. Symptomatic effect on pain relief and improvement of functional disability was also reported with the use of avocado/soybean extracts. Other nutriceuticals, including ginger extracts, should be more extensively investigated. An important issue is that all the conclusive studies with such chemical entities resulted from the use of prescription medicines, and not over-the-counter pills or food supplements.

Topics: Chondroitin Sulfates; Complementary Therapies; Controlled Clinical Trials as Topic; Dietary Supplements; Female; Glucosamine; Humans; Male; Osteoarthritis; Patient Satisfaction; Plant Extracts; Prognosis; Treatment Outcome

There are a sufficient number of short-term studies with these agents suggesting efficacy equal to that seen in the symptomatic treatment of OA using NSAIDs. Two recent meta-analyses by McAlindon and colleagues and Towheed et al reviewed clinical trials of glucosamine and chondroitin in the treatment of osteoarthritis. The study by McAlindon and co-workers included all double-blind placebo-controlled trials of greater than 4 weeks' duration, testing oral or parenteral glucosamine or chondroitin for treatment of hip or knee osteoarthritis. Thirteen trials (six with glucosamine, seven with chondroitin) met eligibility criteria. The authors used global pain score or the Lequesne index in the index joint as the primary outcome measure and considered the trial positive if improvement in the treatment group was equal to or greater than 25% compared with the placebo group, and was significant (P < or = .05). All 13 studies reviewed were classified as positive, demonstrating large effects, compared with placebo (39.5% [S.D. 21.9] for glucosamine, 40.2% [S.D. 6.4] for chondroitin). The authors concluded that clinical trials of these two agents showed substantial benefit in the treatment of osteoarthritis but provided insufficient information about study design and conduct to allow definitive evaluation. Towheed and colleagues reviewed nine randomized, controlled trials of glucosamine sulfate in osteoarthritis. In seven of the randomized controlled trials, in which they compared glucosamine with placebo, glucosamine was always superior. In two randomized controlled trials comparing glucosamine to ibuprofen, glucosamine was superior in one and equivalent in one. Methodologic problems, including lack of standardized case definition of osteoarthritis and lack of standardized outcome assessment led the authors to conclude that further studies are needed to determine if route of administration is important and whether the therapeutic effect is site specific. A meta-analysis of chondroitin sulfate trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or NSAID-controlled trials with 227 patients on chondroitin sulfate were entered into the analysis. All four studies showed chondroitin sulfate to be superior to placebo, with respect to Lequesne index, visual analog scale for pain and medication consumption. Significant changes (P < or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data

Topics: Animals; Chondroitin Sulfates; Clinical Trials as Topic; Collagen; Glucosamine; Humans; Nonprescription Drugs; Osteoarthritis

Osteoarthritis (OA) is the most common form of joint disease. Although OA was previously thought to be a progressive, degenerative disorder, it is now known that spontaneous arrest or reversal of the disease can occur. Conventional medications are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be at least as effective as nonsteroidal anti-inflammatory drugs at relieving the symptoms of OA, and preliminary evidence suggests some of these compounds may exert a favorable influence on the course of the disease.

Topics: Boron; Chondroitin Sulfates; Glucosamine; Humans; Manganese; Niacinamide; Osteoarthritis; Phytotherapy; S-Adenosylmethionine; Vitamins

Successful treatment of osteoarthritis must effectively control pain, and should slow down or reverse progression of the disease. Biochemical and pharmacological data combined with animal and human studies demonstrate glucosamine sulfate is capable of satisfying these criteria. Glucosamine sulfate's primary biological role in halting or reversing joint degeneration appears to be directly due to its ability to act as an essential substrate for, and to stimulate the biosynthesis of, the glycosaminoglycans and the hyaluronic acid backbone needed for the formation of proteoglycans found in the structural matrix of joints. Chondroitin sulfates, whether they are absorbed intact or broken into their constituent components, similarly provide additional substrates for the formation of a healthy joint matrix. Evidence also supports the oral administration of chondroitin sulfates for joint disease, both as an agent to slowly reduce symptoms and to reduce the need for non-steroidal anti-inflammatory drugs. The combined use of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease has become an extremely popular supplementation protocol in arthritic conditions of the joints. Although glucosamine sulfate and chondroitin sulfates are often administered together, there is no information available to demonstrate the combination produces better results than glucosamine sulfate alone.

Topics: Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Humans; Osteoarthritis

Assess the importance of the mid-term placebo effect of symptomatic slow acting drugs given for osteoarthritis.. We analyzed six controlled trials available in the literature. Trial duration ranged from 2 to 6 months. The trials had been conducted to assess the symptomatic effect of diacerhein, avocado/soya unsaponifiable chondrontin sulfate and oxaceprolin given for osteoarthritis of the hip or knee. The main clinical outcomes assessed were functional impairment using the Lequesnes index and a visual analog scale.. Globally, the trials showed decreased function impairment with a 2 to 3 points decrease in the Lequesnes index (15 to 20%) and a 10 to 16 mm fall in the visual analog scale (-20 to -30%) in the placebo groups.. Our findings confirms the importance of the mid-term placebo effect in the clinical course of osteoarthritis in patients given slow-acting drugs. This placebo effect, observed under these circumstances, is an expression of what clinicians will look for in future drugs and should be helpful for calculating the number of patients required in future trials.

Topics: Activities of Daily Living; Aged; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Chondroitin Sulfates; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Placebo Effect; Randomized Controlled Trials as Topic; Research Design; Time Factors; Treatment Outcome

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Humans; Joint Diseases; Keratan Sulfate; Osteoarthritis; Synovial Fluid

Topics: Antibodies, Monoclonal; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Epitope Mapping; Humans; Metalloproteins; Osteoarthritis; Proteoglycans; Synovial Fluid

Chondroprotection is a somewhat new field in the therapy of osteoarthritis, which is designed to improve cartilage repair as well as enhance joint remodeling. It clearly results from both laboratory models as well as from studies on human osteoarthritis, that cartilage contains biological resources to meet the repair of degenerative injuries and inflammation. Interestingly, sulfated glycosaminoglycans from matrix inhibit leukocyte protease and complement-mediated immunological reactions. By fractioning cartilage glycosaminoglycans from Selachus (Matrix), evidence has been obtained that a proper chondroitinsulfate sequence, which is able to inhibit elastase, may be released from cartilage proteoglycans by cleavage of the xyl-ser O-glycosidic bond. Since a number of sulfated glycosaminoglycans have a regulatory function in an array of tissues, attention is drawn to possible regulatory properties of selected sequences of matrix chondroitinsulfate, as far as chondroprotection is concerned.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage; Chondroitin Sulfates; Glycosaminoglycans; Heparin; Humans; Hyaluronoglucosaminidase; Leukocyte Elastase; Osteoarthritis; Pancreatic Elastase; Protease Inhibitors

The remarkable insights into the pathogenesis of osteo-arthrosis (OA) have also affected the therapeutic field. Efforts have been made to find drugs which would somehow block or slow down the evolution of this disease. In this connection, a major contribution has been made by the investigations on glycosaminoglycans (GAGs), which play a crucial role in the physiology of joint cartilage. It was thus suggested that proper supplementation with GAGs might enable chondrocytes to replace the proteoglycans (PG). Galactosaminoglucuronoglycan sulfate (GAGGS) has been used for this purpose. In preliminary clinical trials, GAGGS exhibited a remarkable tolerability and good therapeutic efficacy. GAGs are generally able to inhibit certain enzymes present in the synovial fluid which may damage joint cartilage (elastase, hyaluronidase). Moreover, GAGGS has also been shown to act as an anti-inflammatory drug since it has an inhibitory effect over the complement. All these data supply evidence that, in theory, GAGGS may have a chondroprotective effect in patients with OA. In addition to the positive results of preliminary clinical trials, the use of GAGGS in OA therapy is based on the fact that this drug is absorbed by the body, is concentrated in the cartilages and produces no toxic or teratogenic effects. In the clinical studies performed so far, although of the open type, GAGGS has always yielded clinical improvement both of painful symptoms and of limited function thanks to its proven anti-inflammatory activity. Thus once the results from other ongoing trials (double blind) are available, hopefully GAGGS will in fact become a basic drug for OA therapy.

Topics: Cartilage; Chondroitin Sulfates; Glycosaminoglycans; Humans; Osteoarthritis

Topics: Arthritis, Rheumatoid; Cartilage, Articular; Cathepsins; Chondroitin Sulfates; Collagen; Cyclooxygenase Inhibitors; Glycoproteins; Glycosaminoglycans; Humans; Osteoarthritis; Peptide Hydrolases; Prostaglandins; Protease Inhibitors; Proteoglycans; Water

Topics: Animals; Cartilage, Articular; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Collagen; Dogs; Humans; Keratan Sulfate; Osteoarthritis; Proteoglycans

Topics: Animals; Binding Sites; Cartilage; Cartilage, Articular; Centrifugation, Density Gradient; Chondroitin Sulfates; Collagen; DNA; Hyaluronic Acid; Models, Biological; Osteoarthritis; Protein Conformation; Proteoglycans; Water

The purpose of this study was to compare clinical outcomes obtained with the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane (GCM) supplementation after arthrocentesis plus intraarticular hyaluronic acid (HA) injection. A randomized clinical trial was implemented with adult participants with TMJ-OA who were referred to the author's clinic between February 2014 and May 2015. The sample was entirely composed of patients with TMJ-OA who were treated randomly with a one-session arthrocentesis plus intraarticular HA injection only (control group), or an initial one-session arthrocentesis plus intraarticular HA injection followed by 3 months of GCM supplementation (study group). The predictor variable was management (treatment) technique. The outcome variables were visual analog scale evaluations (masticatory efficiency, pain complaint, joint sound) and mandibular mobility (maximal interincisal opening [MIO], and lateral and protrusive motions of the mandible). The outcome variables were recorded preoperatively and 12 months postoperatively. Thirty-one participants were enrolled in the study. Five were lost during follow-up. The final study sample consisted of 26 participants (age 28.35 ± 10.85 y): 14 in the control group (age 28.71 ± 10.94 y); and 12 in the study group (age 27.92 ± 11.20 y). Pain complaints (p < 0.001) and joint sounds (p = 0.030 for the control group; p = 0.023 for the study group) showed statistically significant decreases. Masticatory efficiency (p < 0.001 for the control group; p = 0.040 for the study group) and lateral mandibular motion (p = 0.040 for the control group; p = 0.004 for study group) showed statistically significant increases in both groups, whereas MIO and protrusive mandibular motion showed no significant changes in either group (p > 0.05). After estimating the differences between the follow-up and baseline outcomes, the mean changes in the primary outcome variables (VAS scores, MIO, and mandibular motion) showed no statistically significant differences between the two groups (p > 0.05). Progressions (reparative remodeling) of hard-tissue TMJ structures were observed on CBCT scans of some participants in both groups. These findings suggested that the use of GCM supplementation after arthrocentesis plus intraarticular HA injection produced no additional clinical benefits or improvements for patients with TMJ-OA compared with arthrocentesis plus intraarticular HA injection alone.

Topics: Adolescent; Adult; Arthrocentesis; Chondroitin Sulfates; Dietary Supplements; Dimethyl Sulfoxide; Glucosamine; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis; Range of Motion, Articular; Sulfones; Temporomandibular Joint; Temporomandibular Joint Disorders; Treatment Outcome; Young Adult

Topics: Aged; Analgesics; Chondroitin Sulfates; Collagen; Dietary Supplements; Female; Glucosamine; Humans; Locomotion; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Measurement; Spain; Treatment Outcome

Osteoarthritis (OA), the commonest joint disorder, is a leading cause of disability. Symptomatic slow-acting drugs for OA (SYSADOA), particularly glucosamine plus chondroitin sulphate (GS/CS), are effective for symptom relief, protect joint cartilage and delay OA progression, with a good safety profile. D-002, a mixture of beeswax alcohols that inhibits both cyclooxygenase and 5-lipoxygenase activities, has been effective in experimental and clinical OA studies, showing also a chondroprotective effect.. To compare the effects of D-002 and GS/SC administered for 12 weeks on OA symptoms.. Participants were randomized to GS/CS (375/300 mg) or 50 mg D-002 once daily for 12 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the Visual Analogy Scale (VAS) scores. The primary outcome was the reduction of the total WOMAC score. Secondary outcomes included WOMAC pain, stiffness and function scores, VAS score and rescue medication consumption.. Of 60 randomized patients, 59 completed the study. D-002 and GS/SC reduced significantly total WOMAC score (72.1% and 78.5%, respectively), and pain, joint stiffness and physical function scores versus baseline. VAS scores decreased significantly with D-002 (76.6%) and GS/SC (76.8%). The reductions, significant from the second week, were enhanced over the trial. Rescue medications were consumed by 3/30 D-002 and 4/30 GS/SC patients. No differences between groups were found. Treatments were well tolerated.. D-002 (50 mg/day) administered for 12 weeks was safe and comparable to GS/SC for alleviating OA symptoms (pain, stiffness, and functional limitation) (RPCEC00000180).

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Drug Therapy, Combination; Fatty Alcohols; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Severity of Illness Index; Treatment Outcome; Young Adult

OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses. ANIMALS 32 healthy 2- to 5-year-old horses. PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups. RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.

Topics: Animals; Chondroitin Sulfates; Drug Therapy, Combination; Female; Glucosamine; Horse Diseases; Horses; Hyaluronic Acid; Injections, Intravenous; Lameness, Animal; Male; Osteoarthritis; Synovial Fluid; Viscosupplements

The article presents the results of prospective longitudinal study. The aim of the study was to investigate influence of complex therapy with chondroitin sulfate on pain and functional disorders in elderly patients with knee osteoarthritis. The study shows sufficient decreasing of pain, stiffness and functional disorders with complex therapy with chondroitin sulfate in comparison with nonsteroidal anti-inflammatory drugs (NSAID) by the second month of therapy with stable effect the next 2 months. All patients decrease their NSAID intake by the end of the study. Satisfaction of complex therapy was high according to patient's and physician's opinion.

Topics: Age of Onset; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Chondroitin Sulfates; Combined Modality Therapy; Drug Monitoring; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Osteoarthritis; Pain Measurement; Patient Education as Topic; Range of Motion, Articular; Risk Factors; Self Care; Severity of Illness Index; Treatment Outcome

A randomized blinded placebo controlled trial was conducted to assess the clinical, biochemical and histological effects of a hyaluronan, sodium chondroitin sulfate and N-acetyl-D-glucosamine combination (PG) administered through an intra-articular (IA) route for the treatment of osteoarthritis (OA) at the time of injury. OA was induced in one carpal joint of each of 16 horses. Horses were designated placebo or IA PG treated. All horses were treated with 125 mg amikacin sulfate IA and 5 mL physiological saline in the middle carpal joint bilaterally on study Days 0 (after induction of OA), 7, 14 and 28, except the OA affected joint of the IA PG horses, which received 5 mL PG plus 125 mg of amikacin sulfate on similar days. Evaluations included clinical and radiographic, synovial fluid analysis, gross and histological examinations, as well as histochemical and biochemical analyses. The model induced a significant pathology that resulted in clinical disease. No adverse treatment-related events were detected in any of the horses. Intra-articular treatment of OA-affected joints with PG resulted in a transient 16% improvement in clinical pain (lameness scores) and evidence of improvement trends in bone proliferation radiographically as well as in the degree of full thickness articular cartilage erosion seen grossly when compared to placebo treated OA affected joints, although the vast majority of outcome parameters were not significantly different than controls. The findings support some potential clinical sign or disease modifying action of this compound administered IA at the tested dose and frequency.

Topics: Acetylglucosamine; Animals; Cartilage, Articular; Chondroitin Sulfates; Drug Combinations; Glycosaminoglycans; Horse Diseases; Horses; Hyaluronic Acid; Lameness, Animal; Osteoarthritis; Sodium Chloride

To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.. This investigator-initiated, single-center, randomized, double-blind, placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0-100-mm visual analog scale (VAS) and functional impairment of at least 6 (0-30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent-to-treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy.. There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores -8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores -2.14; P = 0.008). There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups.. This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile.

Topics: Aged; Chondroitin Sulfates; Double-Blind Method; Female; Hand Joints; Hand Strength; Humans; Male; Middle Aged; Osteoarthritis; Pain; Pain Measurement; Radiography; Treatment Outcome

The purpose is to investigate the effects of chondroitin sulfate and glucosamine on adult patients with Kaschin-Beck disease (KBD). A total of 80 patients, aged over 40 years, were randomized into two groups receiving either 1,600 mg oral mixture of chondroitin sulfate and glucosamine or placebo twice daily for 8 months. Posteroanterior radiographs of bilateral knee in full extension were taken at enrollment and after 8 months. Mean joint-space width of the assigned six points on the tibiofemoral joint compartment was measured by a graduated magnifying lens. The mean joint space decreased significantly in the placebo group (4.3 +/- 1.09 versus 4.1 +/- 1.07 mm, P < 0.0001) after 8 months and was unchanged in the experimental group (P = 0.51). There was no statistical significance in the mean joint space between two groups at baseline and follow-up (P = 0.65 and P = 0.84, respectively). But the overall mean change in joint space was significant between the two groups (P < 0.0001). Knee joint space of the experimental group narrowed slowly compared to the control group. Therefore, chondroitin sulfate and glucosamine might play a protective role in preserving articular cartilage and provide evidence for therapeutic drugs in adult patients with KBD.

Topics: Adult; Chondroitin Sulfates; Dietary Supplements; Double-Blind Method; Drug Combinations; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; T-2 Toxin

Thirty-five dogs were included in a randomised, double-blind, positive controlled, multi-centre trial to assess the efficacy of an orally-administered glucosamine hydrochloride and chondroitin sulfate (Glu/CS) combination for the treatment of confirmed osteoarthritis of hips or elbows. Carprofen was used as a positive control. Dogs were re-examined on days 14, 42 and 70 after initiation of treatment. Medication was then withdrawn and dogs were re-assessed on day 98. Response to treatment was based on subjective evaluation by participating veterinarians who recorded their findings at each visit. Dogs treated with Glu/CS showed statistically significant improvements in scores for pain, weight-bearing and severity of the condition by day 70 (P<0.001). Onset of significant response was slower for Glu/CS than for carprofen-treated dogs. The results show that Glu/CS has a positive clinical effect in dogs with osteoarthritis.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Chondroitin Sulfates; Dog Diseases; Dogs; Double-Blind Method; Drug Therapy, Combination; Female; Glucosamine; Male; Osteoarthritis; Prospective Studies; Statistics, Nonparametric

Rupture of the cranial cruciate ligament (CCL) is one of the most frequent causes of lameness of the rear limb in the dog. Regardless of the type of treatment, CCL rupture inevitably leads to knee osteoarthritis (OA). The purpose of this study was to evaluate the efficacy of associating surgical treatment of spontaneous rupture of the CCL with a chondroprotector, that is called 'supraadditive' because it is formulated to counteract not only chondrodegeneration, but also the oxidative and inflammatory processes of OA. The open-label controlled study used proton NMR spectroscopy to evaluate the synovial fluid of the stifle of 10 dogs with monolateral rupture of the CCL, selected for the study based on specific inclusive criteria. The dogs were assigned randomly into two groups. Five dogs received the supra-additive chondroprotector for 60 days, starting on the day after surgery. Five dogs only underwent surgical reconstruction of the CCL. The results were analysed with the ANOVA unstructured variance matrix-covariance test. The trend over time of the synovial concentration of four metabolites (lactate, alanine, acetyl groups of N-acetylated sugars on glycoproteins and alpha-anomers of glucose) was found to differ to a statistically significant extent between the two groups, suggesting that the supra-additive chondroprotector produces an intra-articular metabolic rebalance. The results support the adjuvant use of the chondroprotector in the management of CCL rupture, in view of its control of the OA changes that accompany this orthopaedic disabling condition.

Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Chondroitin Sulfates; Dogs; Female; Magnetic Resonance Spectroscopy; Male; Osteoarthritis; Plastic Surgery Procedures; Rupture; Synovial Fluid; Treatment Outcome

We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Female; Humans; Keratinocytes; Male; Middle Aged; Osteoarthritis; Psoriasis; Treatment Outcome

The aim of this study was to evaluate the effect of 800 mg/die of chondroitin sulfate (CHS) per os plus naproxen versus naproxen over 2 years in patients with erosive osteoarthritis (EOA) of the hands. Joint count for erosions, Heberden and Bouchard nodes, Dreiser's algofunctional index and physicians' and patients' global assessment of disease activity were studied. A total of 24 consecutive patients (22 women and 2 men, mean age 53.0 +/- 6) suffering from symptomatic OA with radiographic characteristics of EOA were evaluated. The patients were divided into two groups of 12 patients each. The first group took naproxen 500 mg only. The second group was treated with CHS 800 mg orally plus naproxen 500 mg. Joint counts, radiological hand examinations and assessment of disease activity were performed at baseline, at 12 months and at 24 months. In the second year the treated group showed significant worsening in erosion, Heberden, Bouchard and Dreiser scores was recorded. Physician and patient global assessments of disease activity showed no significant difference from baseline scores. The untreated group showed significant worsening in erosion, Heberden and Bouchard nodes, Dreiser index and physician and patient global assessment scores. This study confirms the partial efficacy of oral CHS in improving some aspects of EOA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Drug Therapy, Combination; Female; Finger Joint; Hand Deformities, Acquired; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Pain; Prospective Studies; Radiography; Severity of Illness Index; Treatment Outcome

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

Our objective was to assess the progression of osteoarthritis (OA) using scoring systems based on the anatomical changes recorded in the finger joints on standard radiographs and to test how far these scoring systems could be used to evaluate the effects of candidate "disease modifying osteoarthritis drugs" (DMOAD). The appearance and growth of osteophytes, narrowing of the joint space and subchondral bone changes allowed the classic OA-associated anatomical lesions to be used to score the progression of finger joint OA. Progression of OA in the finger joints was also assessed by the their evolution through previously described and predictable anatomical phases on standard X-rays. These phases were characterised by complete loss of the joint space preceding or coinciding with the appearance of subchondral cysts eroding the entire subchondral plate, and have been described in "inflammatory" or "erosive" OA. The erosive episodes were followed by processes of remodelling. In order to interfere with the progression of osteoarthritis, two chondroitin sulphates with possible DMOAD effects were used in two series of patients with OA of the finger joints. The patients were included in two separate randomised, double-blind placebo-controlled trials: 46 of them received chondroitin polysulphate and 34 received chondroitin sulphate. Eighty-five patients were kept on placebo medication and were used as controls. All 165 patients were followed for 3 years. Posteroanterior X-rays of the metacarpophalangeal and interphalangeal (IP) finger joints were obtained at the start of this prospective study and at yearly intervals thereafter. Almost 80% of the distal IP and 50% of the proximal IP were affected at study entry. In approximately 40% of the patients the classic picture of OA of the IP joints was complicated by manifest erosive OA changes. The two systems to score the progression of OA (Anatomical Lesion and Anatomical Phase Progression Score System) showed definite progression within 3 years of follow-up, especially in the IP joints. When compared with the placebo controls, none of the chondroitin sulphates prevented OA from occurring in previously normal finger joints. However, when the classic OA-associated anatomical lesions were considered, OA was less progressive in both active treatment groups. Furthermore, fewer patients from both chondroitin sulphate- and chondroitin polysulphate-treated groups developed "erosive" osteoarthritis. In conclusion, conventional r

Topics: Adult; Aged; Antirheumatic Agents; Chondroitin Sulfates; Disease Progression; Double-Blind Method; Female; Finger Joint; Humans; Male; Middle Aged; Osteoarthritis; Placebos; Radiography; Risk Assessment

The aim of this study was to evaluate the joint count for erosions in patients with erosive osteoarthritis (EOA) of the hands treated with 800 mg/day of orally administered chondroitin sulfate plus naproxen, compared with that of patients administered naproxen only. Twenty-four consecutive patients (22 women and two men, mean age 53.0 +/- 6) suffering from symptomatic OA and with radiographic characteristics of EOA were studied. The patients were divided into two groups of 12 patients each. The first group took naproxen 500 mg/day only. The second group was treated with chondroitin sulfate 800 mg/day orally plus naproxen 500 mg/day. Radiological hand examinations were performed at baseline and again after 12 and 24 months. In both groups, the joint count for erosions showed a general tendency to increase over time. Progression of erosions at 24 months was lower in patients treated with 800 mg/day chondroitin sulfate plus naproxen than in patients taking naproxen only (p <0.05). Chondroitin sulfate failed to stop the usual time-associated progression in the number of finger joints presenting erosions in EOA of the hands. It was, however, associated with a lower increase in the number of finger joints with erosions detected after 2 years of radiological observation.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Disease Progression; Drug Therapy, Combination; Female; Finger Joint; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Prospective Studies; Radiography; Time Factors

To study clinical effectiveness and tolerance of structum in patients with osteoarthrosis (OA) of the knee joints (KJ) and hip joints (HJ) in a multicenter open randomised trial.. A 6-month trial of effectiveness and tolerance of structum has been performed in 9 medical centers and included outpatients (males and females) with KJ OA or HJ OA satisfying the OA diagnostic criteria of the American Rheumatology College, having x-ray stage I-III according to Kellgren-Lawrence with manifest pain, a total functional Leken index from 4 to 11, regular intake of non-steroid antiinflammatory drugs (NAID) for 30 days in the last 3 months. Consent was obtained from each patient. 192 patients received structum, 363 matched patients served control. Structum was given per os for 3 weeks in a dose of 1.5 g/day then in a dose 1.0 g/day up to 6 months. The patients continued on NAID. The patients' examination was performed in the beginning of the study, at its months 3 and 6.. Leken index in HJ and KJ OA significantly fell after 3 months of structum treatment. Up to month 6 it fell still further (p < 0.05). After 6 months of treatment pain syndrome relieved both at rest and movement, pain at rest disappeared fully in 57% of NJ OA patients and 46% of HJ OA patients, for movement pain it was 17 and 13%, respectively. During the treatment NAID intake was less required in both groups (p < 0.05) while 55% of patients in both groups could discontinue NAID after 6 months of the treatment. Tolerance of the drug was rather good, side effects were mild.. Structum (chondroitin sulphate) is an effective drug for treatment of KJ and HJ OA: it relieves pain, preserves and improves articular function, allows to reduce or discontinue NAID, is well tolerated.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Drug Therapy, Combination; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain Measurement

To study cost-effect efficiency of structum in patients with knee and hip joint osteoarthrosis (OA) in a multicenter trial.. The trial enrolled 192 patients with OA. 110 patients had knee joint OA and 82 patients hip joint OA. The patients received structum for 6 months. Efficacy of the treatment was assessed before use of structum and after it by standard methods. Integral effect of therapy was estimated according to the special program complex. The cost of the drug therapy included the cost of structum and nonsteroid anti-inflammatory drugs (NSAID) on conversion to 1 mg of diclofenac plus the cost of treating side effects. The efficacy per unit cost was calculated by the formula: E1xC2/E2xC1, where E1--integral efficacy of therapy before using structum, E2--integral efficacy of therapy in administration of structum, C1--cost of drug therapy, C2--cost of drug therapy in using structum.. E2 was equal to 94% for knee joints OA and 92% for hip joint OA, E1 and C1--21 and 19%, respectively. C2 was equal to 108.43$ for knee joint OA and 106.97 for hip joint OA, C1--29.3 and 27.44, respectively. The efficacy per unit cost for knee joint OA was 94 x 29.3/21 x 108.3 = 1.21, for hip joint OA 92 x 27.44/19 x 106.97 = 1.24. The figures evidence for much higher efficacy per unit cost of structum vs routine NSAID.. The multicenter trial gave grounds not only for clinical efficacy of structum vs NSAID but also for cost-effect advantage of structum in therapy of OA.

Topics: Chondroitin Sulfates; Costs and Cost Analysis; Female; Hip Joint; Humans; Knee Joint; Male; Osteoarthritis

Previous studies have shown chondroitin sulfate and glucosamine hydrochloride have beneficial effects on symptoms of osteoarthritis of the knee. Our aim was to study the effect of a daily dose of 1500 mg of glucosamine hydrochloride (GH) and 1200 mg of chondroitin sulfate (CS) taken for twelve weeks on subjects diagnosed with capsulitis, disk displacement, disk dislocation, or painful osteoarthritis of the temporomandibular joint (TMJ). Forty-five subjects were enrolled in the study and were randomly assigned to either an active medication group or a placebo group. Eleven subjects were lost from the study for various reasons, resulting in fourteen subjects remaining in the active medication group and twenty subjects remaining in the placebo group. Subjects taking CS-GH had improvements in their pain as measured by one index of the McGill Pain Questionnaire, in TMJ tenderness, in TMJ sounds, and in the number of daily over-the-counter medications needed. Subjects taking the placebo medication had improvements in their pains as measured by the visual analog scale and by four indices of the McGill Pain Questionnaire. Additional studies are required to evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism by which CS-GH affects the articular cartilage of synovial joints.

Topics: Adult; Affect; Analgesics; Analysis of Variance; Bursitis; Cartilage, Articular; Chi-Square Distribution; Chondroitin Sulfates; Double-Blind Method; Drug Combinations; Female; Follow-Up Studies; Glucosamine; Humans; Joint Dislocations; Male; Middle Aged; Movement; Osteoarthritis; Pain Measurement; Pilot Projects; Placebos; Range of Motion, Articular; Statistics as Topic; Temporomandibular Joint Disc; Temporomandibular Joint Disorders

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans due to imbalance between synthesis and degradation. The availability of glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate-limiting for proteoglycan production in cartilage tissue culture. 57 patients suffering from osteoarthritis of the knee were randomized into a group treated for 4 weeks with daily i.v. glucosamine sulfate (GS) together with 800 mg chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on palpation, as well as range of knee motion were then recorded. In the GS group, there was significant reduction of clinical symptoms (p < 0.01), but no significant reduction in the placebo group. Physicians' assessment of tenderness and range of motion were significantly in favor of the GS group (p < 0.01). In those treated with glycosamine there were no adverse reactions and no changes in laboratory blood tests. We conclude that GS can be considered the drug of choice for prolonged treatment of osteoarthritis.

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Female; Glucosamine; Glycosaminoglycans; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Placebos; Prospective Studies; Range of Motion, Articular

A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted.. Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score.. Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects.. The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.

Topics: Activities of Daily Living; Adult; Ascorbic Acid; Chondroitin Sulfates; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Combinations; Glucosamine; Humans; Lumbar Vertebrae; Male; Manganese Compounds; Middle Aged; Military Personnel; Naval Medicine; Osteoarthritis; Osteoarthritis, Knee; Pain; Pilot Projects; Radiography; Running; Surveys and Questionnaires

To study efficiency and tolerance of Structum in gonarthrosis patients as well as duration of its effect after discontinuation.. 100 patients with femorotibial gonarthrosis aged 45 years and older entered an open randomised trial. They had knee joint arthrosis satisfying diagnostic criteria OA ACR at stage II-III according to Kellgren-Lawrence with pain syndrome. Walking pain intensity was > or = 30 mm by the visual analogue scale (VAS), Leken total functional index > or = 4 and < or = 11. Antiinflammatory drugs (AI) were regularly taken for 30 days for the 3 pretreatment months. 50 patients of the study group received Structum and ibuprofen (1200 mg/day) for 6 months. 50 patients of the control group received ibuprofen only. The two groups were followed up for 3 months. Clinical examination was made monthly.. There were significant differences between the groups by the Leken's index (p < 0.005), VAS, pain, daily AI drug requirement. Structum proved more effective. Tolerance was good. Side effects were observed only in two patients (diarrhea and nausea). In the control group, side effects made 15 patients to discontinue the treatment.. Structum is a new effective drug against gonarthrosis which reduces pain, improves joint function. It is well tolerated and allows to diminish the dose of AI drugs. The response to Structum persisted for 3 months after the treatment.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Female; Humans; Ibuprofen; Knee Joint; Male; Middle Aged; Osteoarthritis

This multicenter randomized, double-blind, controlled study was performed to compare the efficacy and tolerability of chondroitin sulfate (CS, Condrosulf, IBSA, Lugano, CH) 1200 mg/day oral gel vs CS 3 x 400 mg/day capsules vs placebo, in patients with mono or bilateral knee osteoarthritis (Kellgren and Lawrence radiographic score grade I to III). A total of 127 patients, 40 of whom were treated with CS 1200 mg/day, 43 with CS 3 x 400 mg/day and 44 with placebo, were included in the statistical analysis of this 3-month treatment study. In the CS groups, Lequesne's Index and spontaneous joint pain (VAS) showed a significant reduction of clinical symptoms (P < 0.01 for both parameters), while only a slight reduction was observed in the placebo group (P = ns for Lequesne's Index and P < 0.05 for VAS). The physician's and patient's overall efficacy assessments were significantly in favour of the CS groups (P < 0.01). The treatment carried out with the three formulations was very well tolerated. In conclusion, these results indicate that CS favours the improvement of the subjective symptoms, improving the joint mobility. An additional consideration is that the efficacy of 1200 mg CS as a single daily dose does not differ from that of 3 x 400 mg daily doses of CS for all the clinical parameters taken into consideration.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Chondroitin Sulfates; Dosage Forms; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Osteoarthritis; Pain Measurement; Treatment Outcome

Patients with osteoarthritis (OA) of the knee were treated with chondroitin sulfate (CS, Condrosulf, IBSA, Lugano, CH) in a randomized, double-blind, placebo-controlled study, performed in two centres. The efficacy and tolerability of oral CS capsules 2 x 400 mg/day vs placebo was assessed in a 6-month study period. Patients with idiopathic or clinically symptomatic knee OA, with Kellgren and Lawrence radiological scores I-III, were included in this trial. Clinical controls were performed at months 0, 1, 3 and 6. Eighty patients completed the 6-month treatment period. Lequesne's Index and spontaneous joint pain (VAS) decreased constantly in the CS group; on the contrary, slight variations of the scores were reported in the placebo group. The walking time, defined as the minimum time to perform a 20-meter walk, showed a statistically significant constant reduction only in the CS group. ANOVA with repeated measures showed a statistically significant difference in favor of the CS group for these three parameters. During the study, patients belonging to the placebo group reported a higher paracetamol consumption, but this consumption was not statistically different between the two treatment groups. Efficacy judgements were significant in favor of the CS group. Both treatments were very well tolerated. All these results strongly suggest that chondroitin sulfate acts as a symptomatic slow-acting drug in knee OA.

Topics: Activities of Daily Living; Administration, Oral; Adult; Aged; Aged, 80 and over; Analysis of Variance; Arthralgia; Chondroitin Sulfates; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain Measurement; Time Factors; Treatment Outcome

A total of 119 patients were included in a randomized, double-blind, placebo-controlled trial in order to assess the S/DMOAD properties in OA of chondroitin sulfate (CS 4&6, 3 x 400 mg/day, Condrosulf IBSA, Lugano, CH). Posteranterior roentgenographies of the interphalangeal (IP) joints were carried out at the start of the study and at yearly intervals. This enabled the investigators to document the radiological progression of the anatomical lesions in the pathological finger joints over a 3-year period. It was shown that the progression of OA in the IP finger joints in an individual can be determined by the evolution of his finger joints through previously described anatomical phases: 'N' (not affected), 'S' (classical OA), 'J' (loss of joint space), 'E' (erosive OA) and 'R' (remodeled joint). Structure/disease-modifying anti-OA drug (S/DMOAD) properties were searched for by assaying the number of patients developing OA in previously normal IP joints ('N' > 'S'), or progressing through the described anatomical phases of the disease ('S' > 'J', 'S' > 'E', 'J' > 'E', 'S' > 'R', 'J' > 'R', 'E' > 'R'). In the CS 4&6 group we observed a significant decrease in the number of patients with new 'erosive' OA finger joints. This result is particularly important since OA of the finger joints becomes a clinical problem (pain, functional loss) when 'S' joints progress to 'J' and especially 'E' phases. During and after these 'E' phases, joints will remodel and show the nodular deformities characteristic of Heberden's and Bouchard's nodes. Treated patients were protected against erosive evolution.

Topics: Aged; Chondroitin Sulfates; Double-Blind Method; Female; Finger Joint; Follow-Up Studies; Humans; Male; Osteoarthritis; Prospective Studies; Radiography; Treatment Outcome

The aim of this study was to assess the clinical, radiological and biological efficacy and tolerability of the SYSADOA, chondroitin 4- and 6-sulfate (CS, Condrosulf, IBSA, Lugano, Switzerland), in patients suffering from knee osteoarthritis. This was a 1-year, randomized, double-blind, controlled pilot study which included 42 patients of both sexes, aged 35-78 years with symptomatic knee OA. Patients were treated orally with 800 mg chondroitin sulfate (CS) per day or with a placebo (PBO) administered in identical sachets. The main outcome criteria were the degree of spontaneous joint pain and the overall mobility capacity. Secondary outcome criteria included the actual joint space measurement and the levels of biochemical markers of bone and joint metabolism. This limited study confirmed that chondroitin sulfate was well-tolerated and both significantly reduced pain and increased overall mobility capacity. Treatment with CS was also associated in a limited group of patients with a stabilization of the medial femoro-tibial joint width, measured with a digitized automatic image analyzer, whereas joint space narrowing did occur in placebo-treated patients. In addition, the metabolism of bone and joint assessed by various biochemical markers also stabilized in the CS patients whereas it was still abnormal in the PBO patients. These results confirm that oral chondroitin 4- and 6-sulfate is an effective and safe symptomatic slow-acting drug for the treatment of knee OA. In addition, CS might be able to stabilize the joint space width and to modulate bone and joint metabolism. This is the first preliminary demonstration that a SYSADOA might influence the natural course of OA in humans.

Topics: Administration, Oral; Adult; Aged; Arthralgia; Chondroitin Sulfates; Double-Blind Method; Female; Humans; Keratan Sulfate; Knee Joint; Male; Middle Aged; Movement; Osteoarthritis; Osteocalcin; Pain Measurement; Pilot Projects; Radiography; Treatment Outcome

To assess the clinical efficacy of chondroitin sulfate (CS) in comparison with the nonsteroidal antiinflammatory drug (NSAID) diclofenac sodium (DS) in a medium/longterm clinical study in patients with knee osteoarthritis (OA).. This was a randomized, multicenter, double blind, double dummy study. 146 patients with knee OA were recruited into 2 groups. During the first month, patients in the NSAID group were treated with 3 x 50 mg DS tablets/day and 3 x 400 mg placebo (for CS) sachets; from Month 2 to Month 3, patients were given placebo sachets alone. In the CS group, patients were treated with 3 x 50 mg placebo (for diclofenac) tablets/day and 3 x 400 mg CS sachets/day during the first month; from Month 2 to Month 3, these patients received only CS sachets. Both groups were treated with 3 x 400 mg placebo sachets from Month 4 to Month 6. Clinical efficacy was evaluated by assessing the Lequesne Index, spontaneous pain (using the Huskisson visual analog scale), pain on load (using a 4 point ordinal scale), and paracetamol consumption.. Patients treated with the NSAID showed prompt and plain reduction of clinical symptoms, which, however, reappeared after the end of treatment; in the CS group, the therapeutic response appeared later in time but lasted for up to 3 months after the end of treatment.. CS seems to have slow but gradually increasing clinical activity in OA; these benefits last for a long period after the end of treatment.

Topics: Acetaminophen; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Diclofenac; Double-Blind Method; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain Measurement; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome

61 patients, suffering from osteoarthritis of the hip, knee and/or finger joints, were included into this open, multicenter, phase IV trial. Patients were treated with chondroitinsulfate (CS) at the recommended dose for 3 months. Concomitant NSAID-therapy, which was necessary for disease control at the beginning of the observation period could be reduced by 72% throughout the 3 months of CS-therapy. The decrease of pain was revealed to be statistically significant; serious side effects were not to be observed during the study. At the beginning of the observation period patients suffered from overall severe pain, and therefore the decrease of pain down to a level, which could not have been achieved by NSAID therapy alone to a greater extent, is of special interest. The results of this trial represent the first office based Austrian data on CS-therapy. In conclusion it could be demonstrated that a significant reduction of the daily NSAID consumption was possible by concomitant CS-therapy, without the risk of deterioration of the patients' symptoms. The 97% compliance does not give evidence for drop-out bias. Moreover, the results of this trial are comparable to other international double-blind, in part placebo-controlled studies, concerning CS-therapy, indicating beneficial results in the treatment of osteoarthritis.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Finger Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Pain Measurement; Treatment Outcome

Chondroitin sulfate (Condrosulf) was characterized for structure, physiochemical properties and purity. This glycosaminoglycan has a relative molecular mass of about 14,000, a sulfate-to-carboxyl ratio of 0.95 due to the high percentage of monosulfated disaccharides (38% 6-monosulfate and 55% 4-monosulfate) and a low amount of disulfated disaccharides (1.1%) inside the polysaccharide chains. No other glycosaminoglycans were detected in the preparation. Chondroitin sulfate was labelled by reduction with sodium 3H-borohydride and administered by oral route in the rat and dog. More than 70% of radioactivity was absorbed and found in urine and tissues. The plasma radioactivity was fractionated by size-exclusion chromatography in three fractions: radioactivity associated with high, intermediate and low molecular mass compounds. The peak value of the concentration of high molecular mass radioactivity compounds in plasma was reached after 1.6 and 2.1 h for the rat and dog, respectively. After 36 h the high molecular mass radioactivity compounds were still present in plasma of dog and rat. After 24 h radioactivity was higher in the intestine, liver, kidneys, synovial fluid and cartilage than in other tissues. Condroitin sulfate was orally administered to man (healthy volunteer) in a single daily dose of 0.8 g and in two daily doses of 0.4 g. The results showed that both forms of administration determined a significant increase of plasma concentration of chondroitin sulfate as compared with predose value over a full 24 h period. Elimination constant values and tmax (of the first administration in the case of fractionated dose) were almost the same for the two administrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Animals; Cattle; Chemical Phenomena; Chemistry, Physical; Chondroitin Sulfates; Chromatography, Gel; Chromatography, High Pressure Liquid; Disaccharides; Dogs; Female; Humans; Male; Middle Aged; Molecular Weight; Osteoarthritis; Rats; Rats, Wistar; Synovial Fluid

Chondroprotection is a somewhat new field in the therapy of osteoarthritis, which is designed to improve cartilage repair as well as enhance joint remodeling. It clearly results from both laboratory models as well as from studies on human osteoarthritis, that cartilage contains biological resources to meet the repair of degenerative injuries and inflammation. Interestingly, sulfated glycosaminoglycans from matrix inhibit leukocyte protease and complement-mediated immunological reactions. By fractioning cartilage glycosaminoglycans from Selachus (Matrix), evidence has been obtained that a proper chondroitinsulfate sequence, which is able to inhibit elastase, may be released from cartilage proteoglycans by cleavage of the xyl-ser O-glycosidic bond. Since a number of sulfated glycosaminoglycans have a regulatory function in an array of tissues, attention is drawn to possible regulatory properties of selected sequences of matrix chondroitinsulfate, as far as chondroprotection is concerned.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage; Chondroitin Sulfates; Glycosaminoglycans; Heparin; Humans; Hyaluronoglucosaminidase; Leukocyte Elastase; Osteoarthritis; Pancreatic Elastase; Protease Inhibitors

Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Chondroitin Sulfates; Humans; Osteoarthritis; Polysaccharides

Based on an analysis of the current data on the pathogenesis of osteoarthrosis, the authors provide evidence for the importance of chondroprotective therapy. Present comparative experimental and clinical (tentative) data on the efficacy of chondroprotective drugs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Tissue Extracts

Clinical trials have been conducted to evaluate the effectiveness of Matrix in osteoarthritis, mainly as regards the advantages offered by its physiological mechanism of action. The experiment, lasting 6 months, was performed on two hundred patients in four different Hospital Departments and one University Center. The results showed a considerable improvement both in pain and in mobility. No relevant side effects were found; only 3% of patients, with oral administration, noticed slight nausea and found it necessary to interrupt treatment.

Topics: Aged; Chondroitin Sulfates; Female; Humans; Male; Middle Aged; Osteoarthritis

To evaluate the efficacy and tolerance of galactosaminoglycuronoglycan sulfate (Matrix vials) in the therapy of tibiofibular arthritis of the knee, forty patients suffering from this illness at radiological stages 1 and 2 undergoing concomitant therapy with NSAIDS, were randomized into two groups of twenty. The treatment group received the drug under study and the control group received placebo. Treatment was carried out in double blind. The therapy protocol comprised 25 intramuscular injections (one injection twice a week). This cycle was repeated for 6 months, for a total of 50 injections. The patients were visited on days 0, 90, 180, 240, 330 and 360. At each visit the following symptoms were evaluated: spontaneous pain, pain on loading, on passive movement and on pressure; changes in NSAIDS posology were also recorded; lastly any possible side effects were noted. Analysis of results has shown a statistically significant higher therapeutic effect on treatment with Matrix for all the symptoms taken into consideration. No important side effects were noted, either local or systemic; in two cases only in the group treated with Matrix and in the same number in the control group slight dyspeptic symptoms were found to occur, but without requiring suspension or reduction in posology. Two patients in the Matrix group and one in the control group left the study for non-compliance with the type of administration. The good clinical results obtained, together with the excellent tolerance shown by the drug, suggest that Matrix may be the drug of choice in the "basic" therapy of osteoarthritis, with its efficacy being demonstrated in an increasing number of clinical studies.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Double-Blind Method; Female; Fibula; Humans; Injections, Intramuscular; Knee Joint; Male; Middle Aged; Osteoarthritis; Tibia

Topics: Aspirin; Chondroitin Sulfates; Clinical Trials as Topic; Drug Synergism; Drug Therapy, Combination; Female; Glycosaminoglycans; Humans; Knee Joint; Middle Aged; Osteoarthritis

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.

Topics: Cartilage; Cartilage, Articular; Cell Differentiation; Cells, Cultured; Chondrocytes; Chondrogenesis; Chondroitin Sulfates; Glycosaminoglycans; Humans; Hydrogels; Osteoarthritis

Defective biosynthesis or function of proteoglycans causes pathological conditions in a variety of tissue systems. Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction caused by imbalanced proteoglycan synthesis and degradation. Identifying agents that regulate proteoglycan metabolism may benefit the development of OA-modifying therapeutics. High-throughput screening (HTS) of chemical libraries has paved the way for achieving this goal. However, the implementation and adaptation of HTS assays based on proteoglycan measurement remain underexploited. Using primary porcine chondrocytes as a model, we report a miniaturized dimethyl-methylene blue (DMMB) assay, which is commonly used to quantitatively evaluate sulfated glycosaminoglycan (GAG) content, with an optimized detection range and reproducibility and its integration with HTS. Treatment with TGF-β1 and IL1-α, known as positive and negative proteoglycan regulators, respectively, supported the assay specificity. A pre-test of chemical screening of 960 compounds identified both stimulators (4.48%) and inhibitors (6.04%) of GAG production. Fluorophore-assisted carbohydrate electrophoresis validated the activity of selected hits on chondroitin sulfate expression in an alginate culture system. Our findings support the implementation of this simple colorimetric assay in HTS to discover modifiers of OA or other diseases related to dysregulated proteoglycan metabolism.

Topics: Animals; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Drug Evaluation, Preclinical; Glycosaminoglycans; High-Throughput Screening Assays; Methylene Blue; Osteoarthritis; Proteoglycans; Reproducibility of Results; Swine

Novel intra-articular nanoreservoirs were implemented employing different cartilage targeting approaches to improve cartilage bioavailability of a chondroprotective drug, cassic acid (CA), for effective amelioration of cartilage deterioration off-targeting CA gastrointestinal disorders. Herein, we compared active cartilage-targeting approach via chondroitin sulfate (CHS) functionalization versus passive targeting using positively charged nanoparticles to target negatively charged cartilage matrix. Firstly, CA integrated nanoreservoirs (CA-NRs) were fabricated based on ionic conjugation between CA and cationic hydrophobic surface modifier octadecylamine (ODA) and were further functionalized with CHS to develop CHS-CA-NRs. Confocal laser microscope was used to visualize the accumulation of nanoparticles into the cartilage tissue. Both targeting approaches promoted CA local cartilage availability and prolonged its residence time. Compared to passive targeted CA-NRs, active targeted CHS-CA-NRs showed higher fluorescence signals in proximity to and inside chondrocytes which lasted for up to 21 days. In MIA-osteoarthritic rats, CHS-CA-NRs showed superior antiosteoarthritic activity, exhibiting highest cartilage repair compared to CA-NRs. Additionally, CHS-CA-NRs significantly inhibited OA inflammatory cytokine, degradation enzyme and oxidative stress and improved cartilage matrix biosynthesis. Conclusively, CHS-CA-NRs improved OA repair showing a superior efficacy for articular cartilage targeting with CHS which could be a potential advance for OA therapy.

Topics: Animals; Anthraquinones; Cartilage, Articular; Chemistry, Pharmaceutical; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Drug Liberation; Lipids; Male; Nanoparticles; Osteoarthritis; Oxidative Stress; Particle Size; Random Allocation; Rats; Rats, Wistar; Surface Properties

Combined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound based on CS and GlcN to treat and/or modulate this disease. The study analyzed the metacarpophalangeal joint of the left thoracic limb of 16 horses divided into two groups, with eight horses treated with CS and GlcN in the treated group (GT) and eight untreated horses in the control group (GC). Chondral lesions were induced through arthroscopy, which was defined as time-point zero (T0). Physical, ultrasonographic, and radiographic examinations and synovial fluid biomarkers measurements were performed on days 0, 30, 60, 90, and 120. At the end of the experiment (T4), arthroscopy was performed again to macroscopically evaluate the joints and collect material for microscopic analysis.. Significant differences were observed between groups in some evaluated parameters, such as visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination. However, the GT still presented slightly improved results for joint flexion angle, analysis of lameness using sensors, and histopathological analysis of chondral repair tissue, however, without the statistical significance (p>0.05).. The treatment was considered effective in the clinical modulation of experimental osteoarthritis, with improvement of some parameters in the GT. However, this type of treatment may not be entirely effective to change the catabolic process in articular cartilage and the progressive induced chondral damage.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Glucosamine; Horse Diseases; Horses; Lameness, Animal; Models, Theoretical; Osteoarthritis; Synovial Fluid

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.

Topics: Chondroitin Sulfates; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Injections, Intra-Articular; Osteoarthritis; Osteoarthritis, Knee; Reactive Oxygen Species; Tyramine; Viscosupplementation; Viscosupplements

Reactive oxygen species (ROS) play a critical role in the pathogenesis of osteoarthritis. The injection of a single antioxidant drug is characterized by low drug utilization and short residence time in the articular cavity, limiting the therapeutic effect of antioxidant drugs on osteoarthritis. Currently, the drug circulation half-life can be extended using delivery vehicles such as liposomes and microspheres, which are widely used to treat diseases. In addition, the composite carriers of liposomes and hydrogel microspheres can combine the advantages of different material forms and show stronger plasticity and flexibility than traditional single carriers, which are expected to become new local drug delivery systems. Chondroitin sulfate, a sulfated glycosaminoglycan commonly found in native cartilage, has good antioxidant properties and degradability and is used to develop an injectable chondroitin sulfate hydrogel by covalent modification with photo-cross-linkable methacryloyl groups (ChsMA). Herein, ChsMA microgels anchored with liquiritin (LQ)-loaded liposomes (ChsMA@Lipo) were developed to delay the progression of osteoarthritis by dual antioxidation. On the one hand, the antioxidant drug LQ wrapped in ChsMA@Lipo microgels exhibits significant sustained-release kinetics due to the double obstruction of the lipid membrane and the hydrogel matrix network. On the other hand, ChsMA can eliminate ROS through degradation into chondroitin sulfate monomers by enzymes in vivo. Therefore, ChsMA@Lipo, as a degradable and dual antioxidant drug delivery platform, is a promising option for osteoarthritis treatment. STATEMENT OF SIGNIFICANCE: Compared with the traditional single carrier, the composite carriers of hydrogel microspheres and liposome can complement the advantages of different materials, which shows stronger plasticity and flexibility, and is expected to become a new and efficient drug delivery system. ChsMA@Lipo not only attenuates IL-1β-induced ECM degradation in chondrocytes but also inhibits the M1 macrophages polarization and the inflammasome activation. The obtained ChsMA@Lipo alleviates the progression of osteoarthritis in vivo, which is promising for osteoarthritis treatment.

Topics: Antioxidants; Chondroitin Sulfates; Delayed-Action Preparations; Humans; Hydrogels; Inflammasomes; Lipids; Liposomes; Microgels; Microspheres; Osteoarthritis; Reactive Oxygen Species

The alteration of the extracellular matrix (ECM) homeostasis plays an important role in the development of osteoarthritis (OA). The pathological changes of OA are mainly manifested in the large reduction of components in ECM, like type II collagen and aggrecan, especially hyaluronic acid and chondroitin sulfate and often accompanied by inflammation. Rebuilding ECM and inhibiting inflammation may reverse OA progression. In this work, we developed new magnesium-containing glycosaminoglycans (Mg-GAGs), to create a positive ECM condition for promoting cartilage regeneration and alleviating OA. In vitro results suggested that the introduction of Mg-GAGs contributed to promoting chondrocyte proliferation and facilitated upregulating chondrogenic genes and suppressed inflammation-related factors. Moreover, Mg-GAGs exhibited positive effects on suppressing synovial inflammation, reducing chondrocyte apoptosis and preserving the subchondral bone in the ACLT-induced OA rabbit model. This study provides new insight into ECM-based therapeutic strategy and opens a new avenue for the development of novel OA treatment.

Topics: Aggrecans; Animals; Cartilage; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Collagen Type II; Extracellular Matrix; Glycosaminoglycans; Hyaluronic Acid; Inflammation; Magnesium; Osteoarthritis; Rabbits

Conventional treatments for osteoarthritis (OA), including drug delivery and tissue engineering approaches, could not offer a high yield of cartilage repair due to the compact and exclusive structure of cartilage. Targeted and high-efficiency delivery of gene sequences is necessary to rebalance the lost homeostatic properties of the cartilage in OA. Herein, we synthesized chitosan (CH)-chondroitin sulfate (CS) nanoparticles (NPs) as a platform for delivering gene sequences. These new nanoparticles benefit from two natural polymers that minimize the toxicity, and the presence of CS can be in favor of targeted delivery. The CAG-GFP plasmid was used as a gene sequence model, and the nanoparticles could successfully encapsulate approximately all of them in their structure. Loaded nanoparticles were characterized in terms of morphology, size, zeta potential, the efficiency of encapsulation and, DNA release pattern. Cell viability and uptake of new nanoparticles were compared to the chitosan nanoparticles and Lipofectamine. After substituting TPP with CS, NPs exhibited a significant decrease in size. In addition, there was little difference in zeta potential between nanoparticles. Furthermore, a tremendous increase in plasmid uptake and cell viability was observed by CH-CS NPs compared to CH-TPP NPs and Lipofectamine. In the final stage, the knockdown level of MMP13 was evaluated with real-time RT-PCR for confirming the potential uptake of CH-CS NPs. The results revealed cellular uptake of siRNA loaded NPs and effective knockdown of MMP13 in chondrocytes. In conclusion, CH-CS nanoparticles can be considered as a candidate for gene therapy purposes in cartilage diseases.

Topics: Chitosan; Chondrocytes; Chondroitin Sulfates; Drug Carriers; Genetic Therapy; Humans; Matrix Metalloproteinase 13; Nanoparticles; Osteoarthritis; Particle Size

Our goals were to identify individuals who required surgery for thumb carpometacarpal (CMC) joint osteoarthritis (OA), determine if CMC joint OA clusters in families, define the magnitude of familial risk of CMC joint OA, identify risk factors associated with CMC joint OA, and identify rare genetic variants that segregate with familial CMC joint OA.. We searched the Utah Population Database to identify a cohort of CMC joint OA patients who required surgery. Affected individuals were mapped to pedigrees to identify high-risk families with excess clustering of CMC joint OA. Cox regression models were used to calculate familial risk of CMC joint OA in related individuals. Risk factors were evaluated using logistic regression models. Whole exome sequencing was used to identify rare coding variants associated with familial CMC joint OA.. We identified 550 pedigrees with excess clustering of severe CMC joint OA. The relative risk of CMC joint OA requiring surgical treatment was elevated significantly in first- and third-degree relatives of affected individuals, and significant associations with advanced age, female sex, obesity, and tobacco use were observed. We discovered candidate genes that dominantly segregate with severe CMC joint OA in 4 independent families, including a rare variant in Chondroitin Sulfate Synthase 3 (CHSY3).. Familial clustering of severe CMC joint OA was observed in a statewide population. Our data indicate that genetic and environmental factors contribute to the disease process, further highlighting the multifactorial nature of the disease. Genomic analyses suggest distinct biological processes are involved in CMC joint OA pathogenesis.. Awareness of associated comorbidities may guide the diagnosis of CMC joint OA in at-risk populations and help identify individuals who may not do well with nonoperative treatment. Further pursuit of the genes associated with severe CMC joint OA may lead to assays for detection of early stages of disease and have therapeutic potential.

Topics: Carpometacarpal Joints; Chondroitin Sulfates; Cluster Analysis; Female; Genetic Predisposition to Disease; Humans; Osteoarthritis; Thumb

An essential component of joint quality is cartilage. Therefore, the protection of this is a prerequisite for maintaining the condition of each joint. The assessment of the presence of articular cartilage is shown by X-ray of both joints in the standing position. Cartilage protection is possible for 1, 2 and 3 degree of cartilage damage according to the Kellgren and Lawrence scale.The challenge for the physician is to identify the cause of OA in accordance with the principles of Evidence Based Orthopedics/Traumatology, and not merely treat symptomatically, which is usually ineffective.In order to objectively present treatment methods, indications and the period of their implementation, it is biologically reasonable to refer to the needs of cartilage tissue resulting from the analysis of the causes of its damage and indications for justified methods of its protection.Biomechanical and biological elements are important in the process of implementing articular cartilage protection.The biomechanical elements are: limb axis disorders, differences in length, distortions at the level of the support quadrilateral, pelvic triangle and shoulder triangle, as well as balance disorders resulting from disturbances in the segmental proportion of the Fi number according to Leonardo da Vinci.There are many biological elements of the discussed disorder and they concern: the state of articular cartilage structure, matrix structure, matrix biophysical elements, molecular sponge mechanism, chondrocytes, cartilage nutrition and the severity of osteoarthritis (OA).The improvement of the conditions of the biological elements of damaged articular cartilage is considered fundamental and concerns the positive impact on numerous cartilage matrix proteins by chondroprotection. This element of treatment consists in the use of chondroitin sulphate and glucosamine as a drug, administered together in the appropriate dose and for a long time depending on the degree of degradation of the articular cartilage, usually from several to several months. The combination of chondroitin sulfate with glucosamine causes the activation of a much larger number of matrix proteins than each of the preparations separately.The pharmacokinetics of chondroitin sulfate and glucosamine are positive and favor their chondroprotective effect.The pharmacoproteomics of chondroitin sulfate and glucosamine administered together result from the activation of as many joint cartilage matrix proteins as possible. The dev

Topics: Cartilage, Articular; Chondroitin Sulfates; Glucosamine; Humans; Matrilin Proteins; Osteoarthritis; Proteomics

Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.

Topics: Animals; Biomimetic Materials; Cartilage, Articular; Chondroitin Sulfates; Hyaluronic Acid; Methacrylates; Osteoarthritis; Swine; Tissue Engineering; Tissue Scaffolds

Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.. Локомотивный синдром (ЛС) это неудовлетворительное состояние пациентов старше 60 лет, которым требуется или может потребоваться посторонняя помощь в ближайшем будущем из-за функционального ухудшения опорно-двигательного аппарата, включающего патологию костной ткани, суставов, мышц и нервной ткани. В реальной клинической практике чаще приходится сталкиваться со следующими проявлениями ЛС: остеоартритом, саркопенией, нарушениями равновесия, хронической скелетно-мышечная болью. На сегодняшний день есть четкое понимание того, что терапия ЛС должна быть долговременной, включать комплексную поддержку мышечной ткани, тренировку баланса, обязательную когнитивно-поведенческую терапию. Максимальная безопасность длительной медикаментозной терапии может быть обеспечена использованием жизненно необходимых микронутриентов, к которым относятся высокоочищенные формы хондроитина сульфата и глюкозамина сульфата, имеющие широкий круг противовоспалительных и регенеративных эффектов.

Topics: Aged; Chondroitin Sulfates; Glucosamine; Humans; Micronutrients; Middle Aged; Osteoarthritis; Syndrome

To determine alterations of chondroitin sulfate (CS) that reflect cartilage damage in an experimental osteoarthritis (OA) model as well as in human OA samples.. Rats were subjected to anterior cruciate ligament transection (ACLT; OA) or a sham procedure and sacrificed 14, 28, or 70 days after ACLT for histopathology and analysis of extracted CS. Cartilage samples from 14 patients undergoing hip or shoulder arthroplasty secondary to OA or fracture (control) were subjected to the same protocol. The CS content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Molar mass (MM) and peak MM of CS were determined using high-performance size-exclusion chromatography (HPSEC).. OA and sham joints at 70 d had 24 [22-24] and 3 [1-6] median histopathology scores, respectively (p < 0.001). Relative CS content (77.7 ± 8.3 µg/mg) was significantly increased in OA samples 70 d after ACLT, as compared to sham (53.5 ± 10.0 µg/mg). Peak MM of CS was higher in OA than in sham samples (P < 0.05). Similarly, CS content and peak MM were higher in cartilage from human OA patients, as compared to fracture samples, reproducing experimental data.. Cartilage matrix from experimental and human OA samples has increased in the relative CS content. Increase in the peak MM distinguishes CS of the extracellular matrix of OA from normal cartilage.

Topics: Animals; Anterior Cruciate Ligament; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Extracellular Matrix; Humans; Osteoarthritis; Rats

The therapeutic potential of using probiotics to treat osteoarthritis (OA) has only recently been recognized, with a small number of animal and human studies having been undertaken. The aim of this study was to describe the effect of a probiotic composition (PB) and chondroitin sulfate (CS), administered separately or in combination, on Tlr2, Tlr4, Nfkb1, and Comp gene expression in cartilage and levels of cytokines (IL-6, IL-8, TGF-β1, IGF-1) and COMP, ACAN, CHI3L1, CTSK, and TLR-2 in serum during monoiodoacetate (MIA)-induced OA in rats. Expression of Tlr2, Tlr4, Nfkb1, and Comp in cartilage was analyzed using one-step SYBR Green real-time RT-PCR. The levels of IL-6, IL-8, TGF-β1, IGF-1, COMP, ACAN, CHI3L1, CTSK, and TLR-2 were measured in serum by enzyme-linked immunosorbent assay. Experimental OA caused an upregulation in Tlr2, Tlr4, Nfkb1, and downregulation of Comp expression in the cartilage. MIA-OA caused a significant increase of TLR-2 soluble form and IL-6, IL-8, TGF-β1, COMP, ACAN, CHI3L1, and CTSK levels in the blood serum; the level of IGF-1, on contrary, decreased. Separate administration of PB and CS raised expression of Comp and reduced Tlr2, Tlr4, and Nfkb1 expressions in cartilage. The levels of the studied markers of cartilage metabolism in serum were decreased or increased (IGF-1). The combined use of PB and CS was more effective than separate application approaching above-mentioned parameters to control. The outcomes of our research prove that multistrain live probiotic composition amplifies the positive action of CS in osteoarthritis attenuation and necessitates further investigation with large-scale randomized controlled trial.

Topics: Animals; Cartilage; Chondroitin Sulfates; Cytokines; NF-kappa B p50 Subunit; Osteoarthritis; Probiotics; Rats; Toll-Like Receptor 2; Toll-Like Receptor 4

Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis.. Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed.. Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group.. In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Topics: Animals; Ascorbic Acid; Body Weight; Boswellia; Chondroitin Sulfates; Dogs; Fatty Acids, Omega-6; Female; Glucosamine; Male; Osteoarthritis; Plant Extracts; Triterpenes; Vitamin E

Osteoarthritis led to the articular cartilage damage and cause different kind of problems - from social to biological. The analysis of existing research unfortunately subjected questioned the reliability of spontaneous regeneration of damaged cartilage, which makes it necessary to focus on the possibilities of protection of the tissue from further its degradation. Treatment of osteoarthritis require to use many drugs, which would lead to slowdown the this process. The aim of below publication is to analyse the practical, clinical biological possibilities of articular cartilage protection with a usage of SYSADOA - (symptomatic slow acting drugs of OA). Osteoarthritis is most frequent disease of the joints and prescription of the SYSADOA should be main principle of that treatment.

Topics: Cartilage, Articular; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Reproducibility of Results

Osteoarthritis (OA) is a degenerative joint disease which is highly prevalent worldwide. However, no therapy for blocking OA pathogenesis is available currently. In this study, chondroitin sulfate (CS) E oligosaccharides were prepared and we identified disaccharide as the functional unit showing the strongest anti-complement activity and screened out complement C5 as its target in the complement system. We determined that CS-E disaccharide produced anti-inflammatory effects to treat OA by regulating the complement system: it inhibited the formation of complement-dependent complexes such as the membrane-attack complex (MAC) by targeting C5 and suppressed MAC-induced protein expression and the activation of downstream MAPK and NF-κB signaling pathways accordingly. By identifying CS-E disaccharide which could be regarded as a complement regulator or inhibitor exhibiting high anti-complement activity and revealing its OA-alleviating mechanism, this study not only provides a new strategy for OA treatment and drug development, but also potentially offers a promising C5 target therapy for other associated diseases.

Topics: Chondroitin Sulfates; Complement C5; Complement Inactivating Agents; Humans; Oligosaccharides; Osteoarthritis

Chondroitin sulfates (CS) account for more than 80% of the glycosaminoglycans of articular cartilage, which impart its physiological functions. We quantified the absolute concentration of the CS components of the full thickness cartilages from the knees of patients with terminal-phase osteoarthritis. Osteochondrol biopsies were removed from the medial femoral condyle and lateral femoral condyle of sixty female patients received total knee arthroplasty, aged from 58 to 83 years old. We found the total CS concentrations and chondroitin-4-sulfate disaccharide were significantly lowered in osteoarthritic samples. Microstructure analysis indicated while chondroitin-0-sulfate was equally distributed across different zones of the osteoarthritic cartilages, chondroitin-4-sulfate is significantly less in the deep zones. Down-regulation of sulfotransferases, the enzymes responsible for CS sulfation, in the lesion site of cartilage were observed. Our study suggested chondroitin-4-sulfate down-regulation can be a diagnostic marker for degraded osteoarthritis cartilage, with potential implications in cartilage regeneration.

Topics: Aged; Aged, 80 and over; Cartilage, Articular; Chondroitin Sulfates; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Osteoarthritis

Osteoarthritis (OA) is a joint affection, defined by articular cartilage demolition, risks of which rise with age. The aim of this study was to compare the efficacy of chondroitin sulfate (CS) course and multistrain live probiotic (LP) administered alone or in combination on the expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane during OA in rats.. OA was induced in male rats by injecting monoiodoacetate (MIA) in right hind knee. Therapeutic groups received 3 mg/kg of chondroprotector (ChP) CS for 28 days and/or 140 mg/kg of LP diet for 14 days. The expression of TLR-2, TLR-4, TNF-α and NF-κB in articular cartilage, subchondral bone and synovial membrane were determined with immunohistochemical staining kits (Thermo Fisher Scientific).. It was established that MIA injection is associated with long-term structural changes in joint tissues that corresponded to OA-like features and associated with activation of pathogen-recognizing molecules and proinflammatory signaling pathways expression. Separate therapy with ChP and probiotics slightly decreased OA score limiting cell death and subchondral bone resorption. However, these changes were not associated with a significant decrease in TLR-2, TLR-4, NF-kB and TNF-α expression. On the other hand, the combination of ChP and LP treatment significantly decreased OA score. This correlated with a decrease in TLR-2, TLR-4, NF-kB and TNF-α expression in chondrocytes and synovial cells.. The outcomes of our research prove that ChPs amplify the positive action of LPs in OA attenuation.

Topics: Animals; Arthritis, Experimental; Cell Proliferation; Chondrocytes; Chondroitin Sulfates; Joints; Male; NF-kappa B; Osteoarthritis; Probiotics; Rats, Wistar; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Osteoarthritis is a degenerative disease that causes substantial changes in joint tissues, such as cartilage degeneration and subchondral bone sclerosis. Chondroitin sulfate and glucosamine are commonly used products for the symptomatic treatment of osteoarthritis. The aim of the present study was to investigate the effects of these products when used as structure-modifying drugs on the progression of osteoarthritis in the rabbit temporomandibular joint. Thirty-six New Zealand rabbits were divided into 3 groups (n = 12/group): control (no disease); osteoarthritis (disease induction); and treatment (disease induction and administration of chondroitin sulfate and glucosamine). Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate. Animals were killed at 30 and 90 days after initiation of therapy. The treatment was effective in reducing disease severity, with late effects and changes in the concentration of glycosaminoglycans in the articular disc. The results indicate that chondroitin sulfate and glucosamine may have a structure-modifying effect on the tissues of rabbit temporomandibular joints altered by osteoarthritis.

Topics: Animals; Arthritis, Experimental; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Drug Therapy, Combination; Extracellular Matrix; Glucosamine; Humans; Injections, Intra-Articular; Injections, Subcutaneous; Iodoacetic Acid; Male; Osteoarthritis; Rabbits; Severity of Illness Index; Temporomandibular Joint

Symptomatic slow-acting drugs (SYSADOA) are increasingly used as effective therapies for osteoarthritis, representing an attractive alternative to analgesics or non-steroidal anti-inflammatory drugs to relieve disease symptoms. Pharmaceutical preparations of chondroitin sulfate, derived from animal sources, alone or in combination with glucosamine sulfate, are widely recognized for their beneficial effect on osteoarthritis treatment. A growing interest has also been devoted to understanding the molecular mechanisms modulated by SYSADOA using -omic strategies, most of which rely on chondrocytes as a model system. In this work, by using an integrated strategy based on unbiased proteomics and targeted cytokine profiling by a multiplexed protein array, we identified differences in the secretomes of human osteoarthritic synoviocytes in response to biotechnological unsulfated, and marine sulfated chondroitins treatments. The combined strategy allowed the identification of candidate proteins showing both common and distinct regulation responses to the two treatments of chondroitins. These molecules, mainly belonging to ECM proteins, enzymes, enzymatic inhibitors and cytokines, are potentially correlated to treatment outcomes. Overall, the present results provide an integrated overview of protein changes in human osteoarthritic synoviocytes secretome associated to different chondroitin treatments, thus improving current knowledge of the biochemical effects driven by these drugs potentially involved in pathways associated to osteoarthritis pathogenesis.

Topics: Aquatic Organisms; Cells, Cultured; Chondroitin Sulfates; Cytokines; Female; Glucosamine; Humans; Middle Aged; Osteoarthritis; Proteome; Synoviocytes

Topics: Chondroitin Sulfates; Glucosamine; Humans; Knee Joint; Osteoarthritis; Rheumatology; United States

The prevalence of osteoarthritis (OA) increases in proportion to age, so in the population of people over 65 years of age. The pathogenesis of OA is based on inflammation of the cartilage tissue of the joint, which leads to damage to the cartilage, activation of signaling pathways and increased levels of cytokines.. To study the literature data on bone and cartilage remodeling with the development of resorptive processes and discuss possible algorithms and recommendations for the management of patients with OA on the background of chondroprotective therapy.. A comprehensive analysis of data presented in open sources, published and available on such resources as PubMed, EMBASE, Cochrane, and Library.. According to the available recommendations and the opinion of experts, among the methods of OA therapy, drugs containing pharmaceutical chondroitin sulfate are currently being discussed, which in a number of studies has demonstrated high antiresorptive effectiveness.. The use of drugs based on pharmaceutical chondroitin sulfate (Chondroguard) contributes not only to the reduction of pain in OA, but also has a positive effect on the processes of inflammation, including those associated with age-related changes in the body.. Распространенность остеоартрита (ОА) увеличивается пропорционально возрасту, так в популяции лиц старше 65 лет. В основе патогенеза ОА лежит воспаление хрящевой ткани сустава, что приводит к повреждению хряща, активированию сигнальных путей и повышению уровня цитокинов. Цель.Изучить данные литературы в отношении ремоделирования костно-хрящевой ткани с развитием резорбтивных процессов и обсудить возможные алгоритмы и рекомендации по ведению больных ОА на фоне хондропротективной терапии. Материалы и методы.Проведен комплексный анализ данных, представленных в открытых источниках, опубликованных и доступных на таких ресурсах, как PubMed, EMBASE, Cochrane, Еlibrary. Результаты.Согласно имеющимся рекомендациям и мнению экспертов обязательным компонентом комплексной терапии ОА являются препараты, содержащие фармацевтический хондроитин сульфат, который в ряде исследований также продемонстрировал высокую антирезорбтивную эффективность. Заключение.Применение лекарственного препарата на основе фармацевтического хондроитина сульфата (Хондрогард) не только способствует уменьшению болевого синдрома при ОА, но и оказывает положительное действие на процессы воспаления, в том числе ассоциированные с возрастными изменениями в организме.

Topics: Aged; Bone and Bones; Chondroitin Sulfates; Cytokines; Humans; Osteoarthritis

To investigate selenium (Se) concentrations in serum of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and Kashin-Beck disease (KBD), together with the effect of Se supplement (chondroitin sulfate [CS] nano-Se [SeCS]) on CS structure-modifying sulfotransferases in KBD chondrocyte. Fifty serum samples from each group with aged-matched (40-60 years), normal control (N), RA, OA, and KBD (25 males and females, respectively) were collected to determine Se concentrations. Furthermore, the KBD chondrocytes were divided into two groups following the intervention for 24 h: (a) non-treated KBD group and (b) SeCS-treated KBD group (100 ng/mL SeCS). The ultrastructural changes in chondrocytes were observed by transmission electron microscopy (TEM). Live/dead staining was used to observe cell viability. The expression of CS-modifying sulfotransferases including carbohydrate sulfotransferase 12, 13, and 15 (CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction and western blotting analysis after SeCS intervention. The Se concentrations in serum of KBD, OA, and RA patients were lower than those in control. In OA, RA, and control, Se concentrations were higher in male than in female, while it is opposite in KBD. In the cell experiment, cell survival rate and mitochondrial density were increased in SeCS-treated KBD groups. Expressions of CHST-15, or CHST-12, and CHST-15 on the mRNA or protein level were significantly increased. Expression of UST slightly increased on the mRNA level, but no change was visible on the protein level. Se deficiency in serum of RA, OA, and KBD was observed. SeCS supplemented in KBD chondrocytes improved their survival rate, ameliorated their ultrastructure, and increased the expression of CS structure-modifying sulfotransferases.

Topics: Adult; Arthritis, Rheumatoid; Chondrocytes; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Middle Aged; Osteoarthritis; Selenium

Oral supplementation of chondroitin sulfate (CS) and glucosamine (GlcN), symptomatic slow-acting molecules, is recommended by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Diseases (ESCEO) and other European Union (EU) guidelines for the restoration of the articular cartilage surface in patients affected by osteoarthritis (OA). They are commercialized as pharmaceutical grade products and as food supplements in combination with plant extracts hyaluronic acid, methylsulfonylmethane, and other components. Food supplements do not need to undergo the strict regulatory controls of pharmaceutical grade products; thus, composition and contaminants that could be present may not be evidenced before commercialization and these uncertainties may give rise to concerns about the bioactivity of these formulations.. In this paper 10 different food supplements (FS) from diverse European countries were analyzed in comparison with two pharmaceutical grade products (Ph) using updated analytical approaches and biochemical cell-based assays. The purity, the titer, and the origin of CS in Ph and FS samples were initially assessed in order to successively compare the biological function. Both food supplements and pharmaceutical formulations were tested in vitro, using the same final CS concentration, on primary chondrocytes and synoviocytes in terms of (i) cell viability, (ii) activation of the NF-κB-mediated inflammation pathway, (iii) cartilage oligomeric matrix protein (COMP-2), IL-6, and IL-8 production.. All the FS presented a certain insoluble fraction; the CS and the GlcN contents were lower than the declared ones in 9/10 and 8/10 samples, respectively. All FS contained keratan sulfate (KS) at up to 50% of the total glycosaminoglycan amount declared on the label. Primary cells treated with the samples diluted to present the same CS concentration in the medium showed cytotoxicity in 7/10 FS while Ph preserved viability and reduced NF-κB, COMP-2, and secreted inflammatory cytokines.. Among all samples tested, the pharmaceutical grade products demonstrated effective modulation of biomarkers counteracting the inflammation status and improving viability and the physiological condition of OA human primary chondrocyte and synoviocyte cells. In contrast to that, most FS were cytotoxic at the tested concentrations, and only 3/10 of them showed similarities to Ph sample behavior in vitro.. This work was partially supported by PON01_1226 NUTRAFAST, MIUR Ministero dell'Università e della Ricerca Scientifica. Bioteknet financed two short-term grants for graduate technicians. The journal's Rapid Service and Open Access fees were funded by IBSA CH.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Dietary Supplements; Europe; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Osteoporosis

Blood cytokines affect the development of inflammatory processes in both normal and pathological states. We have studied changes in the concentration of interleukins (ILs) - 1β, IL-4, IL-10, IL-12B p40, transforming growth factor β (TGF β), tumor necrosis factor (TNF-α) in acute carrageenan-induced inflammation and degenerative-dystrophic changes of knee joint caused by monoiodoacetate-induced Osteoarthritis (OA) in experimental models on rats. We also investigated the change in the cytokine profile during prophylactic and therapeutic administration of chondroitin sulfate to animals under experimental conditions.. The concentration of the cytokines was measured in blood serum by enzyme-linked immunosorbent assay.. The manifestation of articular lesions was characterized by a disturbance in the balance between proinflammatory (IL-1β, IL-12B p40, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF -β) cytokines.. A reduction in the concentration of proinflammatory cytokines in blood serum after prophylactic and therapeutic administration of chondroitin sulfate to the rat with experimental models of acute inflammation of the hind limb and degenerative-dystrophic changes in the knee joint with OA is associated with anti-inflammatory and regenerative properties of the drug.

Topics: Animals; Arthritis, Experimental; Carrageenan; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Edema; Iodoacetic Acid; Male; Osteoarthritis; Random Allocation; Rats; Rats, Wistar; Sensitivity and Specificity

The objective of this study is to investigate changes in the expression of enzymes involved in chondroitin sulfate (CS) sulfation in distal articular surface of proximal interphalangeal joint isolated from school-age children patients with Kashin-Beck disease (KBD), using normal children as controls. Articular cartilage samples were collected from four normal and four KBD children (7-12 years old), and these children were assigned to control and KBD groups. Hematoxylin and eosin (H&E), toluidine blue (TB), and immunohistochemical (IHC) stainings were utilized to evaluate changes in joint pathology and expression of enzymes involved in CS sulfation, including carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), and uronyl 2-O-sulfotransferase (UST). The correspondence results were examined by semi-quantitative analysis. Compared with the control group, the KBD group showed the following: a significant decrease of total chondrocytes in superficial, middle, and deep layers and deposition of sulfated glycosaminoglycans in extracellular matrix of KBD cartilage were observed; positive staining chondrocytes of CHST-12, CHST-13, and UST were significantly less in superficial zone of KBD cartilage; and CHST-13 positive staining chondrocytes was reduced in deep zone of KBD cartilage. In contrast, the positive staining rates of CHST-12, CHST-13, and UST in KBD were significantly higher than those in the control group. The decreased expression of these enzymes and the physiologic compensatory reaction may be the signs of early-stage KBD. The alterations of CS structure modifying sulfotransferases in finger articular cartilage might play an important role in the onset and pathogenesis of school-age KBD children.

Topics: Cartilage, Articular; Child; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Osteoarthritis; Selenium; Sulfotransferases

Osteoarthritis (OA) affects the integrity of the entire joint including the synovium. The most abundant cells in the synovium are fibroblasts (SF). Excessive mechanical loading might contribute to OA pathogenesis. Here, we investigate the effects of mechanical loading on SF derived from non-OA (N-SF) and OA patients (OA-SF). We treated N-SF and OA-SF with or without mechanical loading for 48h after 24h of preincubation. Then we assessed gene and protein expression of proinflammatory factors (TNFα, COX-2, PG-E2, IL-6), extracellular matrix (ECM) components (COL1, FN1) and glycosaminoglycans (GAGs) via RT-qPCR, ELISA, DMMB assay and HPLC. Mechanical loading significantly increased TNFα and PG-E2 secretion by N-SF and OA-SF, whereas in OA-SF IL-6 secretion was reduced. COL1 and FN1 secretion were downregulated in N-SF during loading. OA-SF secreted less COL1 compared to N-SF under control conditions. In contrast, OA-SF in general expressed more FN1. GAG synthesis was upregulated in N-SF, but not in OA-SF during loading with OA-SF displaying a higher charge density than N-SF. Mechanical loading enhanced proinflammatory factor expression and GAG synthesis and decreased secretion of ECM components in N-SFs, indicating a contributing role of SF to OA development.

Topics: Adult; Aged; Chondroitin Sulfates; Female; Fibroblasts; Glycosaminoglycans; Humans; Inflammation; Male; Middle Aged; Osteoarthritis; Reverse Transcriptase Polymerase Chain Reaction; Stress, Mechanical; Synovial Membrane

Magnesium chondroitin sulfate (MgCS) has been fabricated and characterized in this study. We investigated its morphology, composition as well as structure. The results verify that the sodium of sodium chondroitin sulfate (CS) is successfully replaced by magnesium and formed a polysaccharide-metal ion complex. To evaluate the clinical potential of MgCS, cell proliferation and apoptosis test were conducted. The results reveal that MgCS could effectively increase the proliferation and decrease the apoptosis of osteoarthritis (OA) chondrocytes. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to evaluate the gene expression level. RT-qPCR analysis suggests that MgCS could significantly increase the expression of COLII and decrease the expression of IL-1β and iNOS in OA chondrocytes. Furthermore, significant upregulation of Bcl-2 mRNA expression and downregulation of the expression of apoptosis related gene p53 were observed. Thus, it is indicated that MgCS should have great potentials in OA treatment.

Topics: Apoptosis; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Dose-Response Relationship, Drug; Humans; Magnesium; Osteoarthritis

This study aimed to provide evidence for understanding how to treat osteoarthritis (OA) in our country. Therefore, it was necessary to match information and investigations related to the treatment of the disease from the three main types of specialists involved: physiatrists, orthopedists and rheumatologists.. The authors acted as a scientific advisory committee. From the initial discussions, a structured questionnaire was developed for use with a group of specialists on OA using the Delphi technique. The questionnaire was sent to 21 experts appointed by the authors, and the results obtained were critically analyzed and validated.. The prevalence of OA was 33% in Brazil, corresponding to one-third of the individuals in the reference population, which included individuals over 25 years of age. Another significant finding was that most patients did not receive any form of treatment in the early stages of OA.. The committee pointed to the need for early intervention and that the available medicinal resources can fulfil this important role, as is the case with SYSADOA treatments. Glucosamine-based medicinal products with or without chondroitin could also fulfill this need for early treatment. The other generated evidence and included investigations were then grouped together and are the subject of this publication.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Chondroitin Sulfates; Clinical Competence; Consensus; Delphi Technique; Drug Therapy, Combination; Evidence-Based Medicine; Female; Glucosamine; Humans; Male; Middle Aged; Orthopedics; Osteoarthritis; Osteoarthritis, Knee; Physical and Rehabilitation Medicine; Practice Guidelines as Topic; Rheumatology; Severity of Illness Index; Treatment Outcome

Topics: Animals; Apoptosis; Caspases; Cell Survival; Chondrocytes; Chondroitin Sulfates; Disease Models, Animal; DNA Fragmentation; Humans; Hydrogen Peroxide; Mitochondria; Mitochondrial Dynamics; Osteoarthritis; Rats

Chondroprotectors (CP) are biological agents that contribute to the regeneration of the cartilage surfaces, joint capsule, participating in the metabolism of the articular cartilage. Progressive loss of hyaline cartilage and a decrease in chondroitin sulfate (CS) is observed in osteoarthritis (OA) including low back pain. OA therapy is aimed at slowing disease progression, relief of pain symptoms, reduction of functional disorders. With this purpose, orally or injectable CP (chondroguard) are used. The optimal dosing regimen for the parenteral forms of CP is recommended: 3 injections of 1 ml (100mg) of chondroguard introduction for 1 week, 2 ml (200mg) from the 4-th injection, 25-30 injections at 200 mg in a day, with a second 6 month course.. Хондропротекторы - биологические препараты, которые способствуют регенерации хрящевых поверхностей и суставной сумки, участвуя в обменных процессах суставного хряща. Прогрессивная потеря гиалинового хряща, уменьшение количества хондроитина сульфата наблюдаются при остеоартрозе различной локализации, в том числе при дорсопатии. Терапия остеоартроза направлена на замедление прогрессирования заболевания, облегчение болевых симптомов, уменьшение функциональных нарушений. С этой целью назначают пероральные или инъекционные формы хондропротекторов (хондрогард). Оптимальный режим дозирования при назначении парентеральных форм хондропротекторов: хондрогард внутримышечно первые 3 инъекции по 1 мл (100 мг), начиная с 4-й инъекции - по 2 мл (200 мг), 25-30 инъекций по 200 мг внутримышечно через день, повторный курс через 6 мес.

Topics: Cartilage, Articular; Chondroitin Sulfates; Humans; Injections; Low Back Pain; Osteoarthritis

Chondroitin sulfate and glucosamine, commercialized as anti-osteoarthritis food supplements, do not undergo the strict quality controls of pharmaceuticals. In this paper a systematic multi-analytical approach was designed to analyse 25 food supplements from 8 European countries compared to 2 pharmaceuticals by using high performance anion-exchange chromatography with pulsed amperometric detection, size exclusion chromatography with triple detector array, capillary electrophoresis, mono and bi-dimensional NMR. Furthermore the biological activity was assessed on in vitro human synoviocyte and chondrocyte primary cell models. Most of the samples (over 19 out of 25) showed lower condroitin sulfate and glucosamine contents than the declared ones (up to -60.3%) while all of them showed a KS contamination (up to 47.1%). Mixed animal origin chondroitin sulfate and multiple molecular weight species were determined in more than 32% of the samples. Only 1 on 5 biologically screened samples had an effective action in vitro almost comparable to the pharmaceuticals.

Topics: Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Dietary Supplements; Drug Contamination; Europe; Glucosamine; Humans; Keratan Sulfate; Osteoarthritis; Synoviocytes

Osteoarthritis (OA) is a common joint disease characterized by cartilage degradation. Chondroitin sulfate from shark (CS-S) has a good effect on OA in clinical, but due to source limited of CS from shark. Therefore, it is important to find a novel CS source with similar efficacy to CS-S in the treatment of OA. Herein, we reported a therapeutic effect of CS from scophthalmus maximus (CS-SM) for treating OA in rats. The OA model was established. After intervention with CS-SM by intragastric administration. Our results showed that CS-SM could protect articular cartilage in OA, inhibit the degradation of cartilage, decrease the apoptosis of chondrocytes, decline the content of interleukin-1, tumor necrosis factor-α and Prostaglandins E

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Flatfishes; Gene Expression Regulation; Male; Matrix Metalloproteinase 1; Osteoarthritis; Rats; Synovial Fluid; Tissue Inhibitor of Metalloproteinase-1

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48 h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

Topics: Animals; Chondrocytes; Chondroitin Sulfates; Collagen Type II; Combined Modality Therapy; Disease Models, Animal; Glucosamine; Immunohistochemistry; Interleukin-10; Interleukin-1beta; Low-Level Light Therapy; Male; Osteoarthritis; Rats, Wistar

Liposomes are promising systems for the delivery of macromolecules and poorly absorbed drugs, owing to their ability to compartmentalize drugs, their biodegradability and biocompatibility.. The aim of the present study was to formulate and evaluate conventional and modified glucosamine sulphate (GluS) and chondroitin sulphate (CS) liposomal formulations, to enhance their oral permeation for the treatment of osteoarthritis (OA).. Liposomal formulations were prepared by the thin-film hydration method using two types of phospholipids; Epikuron 200© and Epikuron 200© SH, and three permeation enhancers; poloxamer 407, cetylpyridinium chloride, and sodium deoxycholate. In-vitro characterization of liposomal formulations was conducted in terms of entrapment efficiency, particle size, zeta potential, viscosity, physical stability and mucoadhesive strength. Surface morphology and vesicle shape, ex-vivo intestinal permeation, and histopathological studies were further carried out on the selected formulation.. Results showed that the liposomal formulation containing sodium deoxycholate was the most optimum formula, showing high entrapment efficiency (60.11% for GluS and 64.10% for CS) with a particle size of 4.40 µm, zeta potential of -17.2 mV and viscosity of 2.50 cP.. The aforementioned formula displayed the highest cumulative % permeated of GluS and CS through rabbit intestinal mucosa compared to the solution of drugs and other liposomal formulations (64.20% for GluS and 78.21% for CS) after 2 hours. There were no histopathological alterations in the intestinal tissue, suggesting the safety of the utilized liposomal formulation. In light of the above, liposomes can be considered promising oral permeation-enhancer system for GluS and CS, which is worthy of future bioavailability experimentation.

Topics: Animals; Chondroitin Sulfates; Deoxycholic Acid; Dietary Supplements; Glucosamine; Intestine, Small; Liposomes; Osteoarthritis; Particle Size; Permeability; Rabbits; Viscosity

Chondroitin sulfate (CS) is an important component of the extracellular matrix of cartilage and has been widely used as one of the main drugs for the treatment of joint pain-related nutraceuticals and medicines. Sturgeon bone (SB) is the main waste during deep processing of sturgeons in fishery production. The present study was evaluated the therapeutic effect of CS from SB (CSSB) on monosodium iodoacetate (MIA)-induced osteoarthritis (OA) pain and further explored the potential medicinal value of CSSB. The OA pain model was induced by intra-articular injection of MIA and then treated with CSSB. The results showed that, on the organismic level, CSSB can significantly reduce the joint swelling, reduce the pathological injury of the joints, decrease the levels of IL-1, TNF-α and PGE

Topics: Analgesics; Animals; Arthralgia; Arthritis, Experimental; Biological Products; Biomarkers; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Inflammation Mediators; Iodoacetates; Male; Osteoarthritis; Rats

Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and the leading cause of joint disability in elderly patients. In this study, we fabricated strontium chondroitin sulfate (SrCS), a new polysaccharide-metal ion complex that is the combination of chondroitin sulfate and strontium, which are two widely adopted chemicals in OA clinical management. The structural, chemical compositions and morphology of as-fabricated SrCS were systematically investigated. Cell proliferation test, RT-PCR and preliminary animal studies were conducted to evaluate the clinical potential of SrCS on OA treatment. The materials characterization results verified that the Sr was successfully integrated into CS by replacing sodium in the original structure and formed a new polysaccharide-metal ion complex. The cell proliferation results indicated that the SrCS has excellent biocompatibility for both chondrocyte and osteoblast. The RT-PCR results showed that the SrCS can significantly increase the expression of COLII and ACAN, decrease MMP1 and MMP13 in chondrocyte and decrease the IL-6 and IL-1β in both chondrocyte and osteoblast. Preliminary animal studies demonstrated that SrCS can effectively simulate the articular cartilage formation in SD-rats after modified Hulth's OA modeling surgery. We therefore believed that the SrCS should be a rather effective chemical for OA clinical management as well as a beneficial component for various biomaterials in cartilage tissue engineering.

Topics: Animals; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Humans; Osteoarthritis; Rats; Strontium

The present work showed the biofabrication of platinum nanoparticles (PtNPs) using chondroitin sulfate via a facile, eco-friendly route by just heating leaf extract and H

Topics: Chondroitin Sulfates; Humans; Metal Nanoparticles; Osteoarthritis; Platinum; X-Ray Diffraction

To investigate the expression of enzymes involved in chondroitin sulfate (CS) sulfation in the articular cartilage isolated from adult patients with osteoarthritis (OA) and Kashin-Beck disease (KBD), using normal adults as controls.. Articular cartilage samples were collected from normal, OA and KBD adults aged 38-60 years old, and divided into three groups with six individual subjects in each group. The morphology and pathology grading of knee joint cartilage was examined by Safranin O staining. The localization and expression of enzymes involved in CS sulfation (CHST-3, CHST-11, CHST-12, CHST-13, carbohydrate (N-acetylgalactosamine 4-sulfate 6-O) sulfotransferase 15 - CHST-15, and uronyl 2-O-sulfotransferase - UST) were examined by immunohistochemical (IHC) staining and semi-quantitative analysis.. Positive staining rates for anabolic enzymes CHST-3, CHST-12, CHST-15, and UST were lower in the KBD and OA groups than those in the control group. Meanwhile, reduced levels of CHST-11, and CHST-13 in KBD group were observed, in contrast to those in OA and control groups. The expressions of all six CS sulfation enzymes were less detected in the superficial and deep zones of KBD cartilage compared with control and OA cartilage.. The reduced expression of the CS structure modifying sulfotransferases in the chondrocytes of both KBD and OA adult patients may provide explanations for their cartilage damages, and therapeutic targets for their treatment.

Topics: Adult; Carbohydrate Sulfotransferases; Cartilage, Articular; Case-Control Studies; Chondroitin Sulfates; Female; Humans; Kashin-Beck Disease; Male; Middle Aged; Osteoarthritis; Sulfotransferases

In previous in-vitro and ex-vivo studies we proved the specific uptake of (99m)Tc radiolabeled chondroitin sulfate (CS) in human articular cartilage. As a logical next step for the clinical use for imaging osteoarthritis we investigated in-vivo uptake of (99m)TcCS in dogs.. The radiolabeling of CS Condrosulf (IBSA, Lugano, Switzerland) was performed using 25mg of CS and 20-40MBq/kg body weight of (99m)Tc by means of the tin method. In-vivo uptake of (99m)TcCS was evaluated in dogs (n=12, castrated males, 4-9years, with 15-51kg body weight). 6 healthy dogs served as controls and 6 with clinical and radiological signs of osteoarthritis in the carpal, elbow, and tarsal joint were examined. The tracer was i.v. injected into the external cephalic vein. The uptake was monitored after 2, 4, 6 and 24h in healthy and osteoarthritic dogs using a planar gamma camera by regional planar or whole body ventral and dorsal acquisition. For whole body scintigraphy animals were under general anesthesia, for planar under sedation only.. In healthy control dogs we did not detect any specific uptake of (99m)TcCS in the cartilage. In contrast, in the diseased dogs suffering from osteoarthritis a significant, specific, persistent uptake between 4 and 6h in tarsal, carpal and cubital joints was documented. Median target (joint) to background (mid antebrachium) ratio (T/B) in the OA joints after 4, 6, and 24h was significantly higher than in healthy controls. Target to background ratio using soft tissue as a background (T/S) a similar significantly higher than in healthy controls. In all osteoarthritic joints we found a significant positive correlation (r=0.8, n=20) between grade of disease (I-III) and T/B. When matching radiographic (X ray) changes in osteoarthritic joints (grade II and III) we found also a maximal uptake of (99m)TcCS at the specific anatomical site of highest cartilage degeneration. None of the dogs experienced any side effects.. These results suggest that (99m)TcCS might become a promising diagnostic tool for imaging osteoarthritis. More extensive and detailed examinations are required, however, before extending this methodology for application in humans.

Topics: Animals; Biological Transport; Cartilage, Articular; Chondroitin Sulfates; Dogs; Humans; Isotope Labeling; Male; Molecular Imaging; Osteoarthritis; Quality Control; Technetium; Tissue Distribution

Chondroitin sulfate (CS) plays important roles in the complement system. However, the CS structure is complicated due to different sources and the number and positions of sulfate groups. The objective of this study was to prepare different low molecular weight chondroitin sulfates (LMWCSs) and to investigate the biological activity in anti-complement capacity. A series of LMWCSs was prepared from different sources and characterized by ultraviolet-visible (UV) spectroscopy, high-performance liquid chromatography (HPLC), size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) and nuclear magnetic resonance (NMR) spectroscopy. Hemolytic, anti-complement 3 deposition capacity and cell viability assays were carried out to investigate the biological activities in vitro. The results showed that LMWCS prepared from shark cartilage with the oxidative degradation method (LMWCS-S-O) had the best anti-complement capacity. LMWCS-S-O could inhibit the alternative pathway of the complement system and protect chondrocytes from cell death. The attenuating effect of LMWCS-S-O on Osteoarthritis (OA) was investigated by destabilization of the medial meniscus (DMM) model in vivo. Functional wind-up, histological and C5b-9 analyses were used to evaluate the treatment effect on the OA model. In vivo results showed that LMWCS-S-O could attenuate OA. LMWCS-S-O with a high content of ΔDi-2,6diS and ΔDi-6S could be used for attenuating OA through regulating the complement system.

Topics: Animals; Cell Survival; Chondrocytes; Chondroitin Sulfates; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Molecular Weight; Osteoarthritis; Random Allocation; Treatment Outcome

Chondroitin is an organic compound, belonging to the group of glycosaminoglycans. In the treatment of degenerative joint disease, aka osteoarthritis, chondroitin sulphate is applied as a medicine or a dietary supplement. The biological importance of chondroitin sulphate has been already largely determined. The newest data on glycobiology research suggest that proteoglycans, as well as their complex polysaccharide macroparticles not only are the structural elements, but also they participate in multiple metabolic processes at a molecular level as well as in the physiological processes, regulating this type of mechanisms. The preparations applied in the treatment of degenerative joint disease, containing chondroitin sulphate, are attributed numerous therapeutic and chondroprotective properties including stabilizing synthesis processes and cartilage degradation through stimulation and inhibition of chondrocyte apoptosis (production of the elements of the intracellular substance and osteocyte stimulation), an increased proteoglycan and hyaluronic acid biosynthesis, inhibition of the activity of proteolytic enzymes and hyaluronidase, reduction of inflammatory mediators (prostaglandins and leukotrienes) and a decreased collagen II degradation. Based on the results of the multidirectional research available in the newest source literature, the analysis of the therapeutic efficacy and safety of chondroitin application in the treatment of degenerative joint disease was conducted.

Topics: Chondroitin Sulfates; Humans; Osteoarthritis; Treatment Outcome

Osteoarthritis (OA) is a degenerative joint disease, which has no complete treatment with medication yet. Intraarticular hyaluronan (HA) injection can decrease pain and modify the natural course of OA. This study was designed to provide long term delivery of an MMP (matrix-metalloproteinase) inhibitor agent-doxycycline, together with matrix regenerative agent-chondroitin sulfate for treating OA which progress with matrix degenerations. Doxycycline (D) and doxycycline-chondroitin sulfate (D-CS) loaded poly-ɛ-caprolactone (PCL) microspheres (MS) were prepared as intraarticular delivery systems. Bio-effectiveness of developed microspheres was first evaluated with three-dimensional in vitro model of OA where both MS showed significant reduction in MMP-13 levels compared to untreated OA-chondrocytes at 15 and 24 days. Significant decrease was observed in GAG release into the media for both D MS and D-CS MS treated groups at 15 and 24 days. Second, the microspheres were injected to rabbit knee in hyaluronan (HA) to evaluate the effectiveness of the treatment. Radiographic scores of D MS and D-CS MS groups improved after 8 weeks when compared to OA group. Mankin-Pitzker histological scores similarly showed improvement with D MS and D-CSMS groups when compared to OA group. Ex vivo hardness tests of cartilages demonstrated superior hardness values with both doses of D-CSMS compared to OA group. D MS showed promising improvement of OA in histology results. Although, both MS groups had similar effects on cells in the in vitro model, D-CSMS had a positive contribution on all in vivo treatment outcomes and showed potential as a new strategy for treatment when applied to OA knee joints.

Topics: Animals; Chondroitin Sulfates; Disease Models, Animal; Doxycycline; Drug Evaluation, Preclinical; Injections, Intra-Articular; Microspheres; Osteoarthritis; Rabbits

Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages.

Topics: Animals; Carboxymethylcellulose Sodium; Cartilage, Articular; Cattle; Cell Death; Cell Survival; Chondrocytes; Chondroitin Sulfates; Collagenases; Drug Evaluation, Preclinical; Hyaluronic Acid; Osteoarthritis; Propane; Riboflavin; Tyramine; Ultraviolet Rays

This study investigates the effect of a new combination of glucosamine hydrochloride, chondroitin sulfate, methylsulfonylmethane, Harpagophytum procumbens root extract (standardized to 3% harpagoside) and bromelain extract (GCMHB) on formalin-induced damage to cartilage tissue in the rat knee joint and evaluates this combination in comparison with another combination of glucosamine hydrochloride, chondroitin sulfate and methylsulfonylmethane (GKM).. Animals in the control group were injected with formalin into the knee joint (FCG). Animals in the GCMHB-500 group were given 500mg/kg GCMHB+formalin, and those in the GKM-500 group were given 500mg/kg GKM+formalin. Finally, a healthy group (HG) was also used. GCMHB and GKM were administered to rats orally once a day for 30days. At the end of this period, the rats were sacrificed and the levels of MDA, NO, 8-OH/Gua, and tGSH in the knee joint tissue were measured. Analysis of IL-1β and TNF-α gene expression was done and the tissue was evaluated histopathologically.. MDA, NO and 8-OH/Gua levels and IL-1β and TNF-α gene expression were significantly lower in the GCMHB-500 group compared to the FCG group, whereas tGSH was significantly higher in the GCMHB-500 group than in the FCG group. No significant difference was found for the IL-1β, TNF-α and oxidant/antioxidant parameters between the GKM and FCG groups. The histopathological analysis showed that GCMHB could prevent damage to the cartilage joint, whereas GKM could not.. GCMHB may be used clinically by comparing with GKM in the treatment of osteoarthritis.

Topics: Animals; Bromelains; Cartilage; Chondroitin Sulfates; Dimethyl Sulfoxide; Disease Models, Animal; Drug Combinations; Formaldehyde; Gene Expression Regulation; Glucosamine; Harpagophytum; Interleukin-1beta; Knee Joint; Male; Osteoarthritis; Plant Extracts; Rats; Rats, Wistar; Sulfones; Tumor Necrosis Factor-alpha

Osteoarthritis is thought to be the most prevalent chronic and disabling joint disease in animals and humans and its treatment is a major orthopaedic challenge because there is no ideal drug treatment to preserve joint structure and function, as well as to ameliorate the symptomatology of the disease. The aim of the present study was to assess, using histology, histomorphometry and micro-CT, the effects of the treatment with several drugs of the SYSADOA group and a bisphosphonate in a model of early osteoarthritis, comparing all the results obtained.. Osteoarthritis was surgically induced by anterior cruciate ligament transection and partial meniscectomy on one knee of 56 rabbits; treatment was started three weeks after surgery and lasted 8 weeks; at the end of this period, the animals were sacrificed. Animals were divided into seven groups (8 animals each), one for each regimen of treatment (glucosamine sulfate, chondroitin sulfate, hyaluronic acid, diacerein, risedronate and a combination of risedronate and glucosamine) and one for the control (placebo-treated) group. Following sacrifice, femoral osteochondral cylinders and synovial membrane samples were obtained for their evaluation by qualitative and quantitative histology and micro-CT.. The model induced osteoarthritic changes in the knee joints and none of the treatments showed a significantly better efficacy over the others. Regarding cartilage thickness and volume, all the treatments achieved scores halfway between control groups, without statistical differences. Regarding the synovial membrane, diacerein and risedronate showed the best anti-inflammatory profile, whereas glucosamine and chondroitin did not present any effect standing the hyaluronic acid results between the others. Regarding the subchondral bone, there were no differences in thickness or volume, but risedronate, diacerein and hyaluronic acid seemed to have considerably modified the orientation of the trabecular lattice.. Out of the different drugs evaluated in the study for OA treatment, diacerein and risedronate showed, in all the parameters measured, a better profile of effectiveness; hyaluronic acid ameliorated cartilage swelling and promoted bone formation, but with a poor synovial effect; and finally, chondroitin and glucosamine sulfate prevented cartilage swelling in a similar way to the others, but had no effect on cartilage surface, synovial membrane or subchondral bone.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Arthrography; Bone Density Conservation Agents; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Drug Therapy, Combination; Female; Femur; Glucosamine; Hyaluronic Acid; Joints; Osteoarthritis; Rabbits; Risedronic Acid; Synovial Membrane; Tomography, X-Ray Computed

To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins.. Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1β, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale.. A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05).. The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.

Topics: Aged; Arthralgia; Chondroitin Sulfates; Female; Follow-Up Studies; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Osteoarthritis; Pain Measurement; Prospective Studies; Recurrence; Severity of Illness Index; Time Factors; Vascular Endothelial Growth Factor A

Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396±2.7nm, showed extended release up to 16h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8±1.23μg/ml) than that of drug dispersion (2.9±0.45μg/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA.. This study demonstrates the feasibility of targeted delivery of diacerein to articular tissue using soluble polysaccharide chondroitin sulfate as the targeting vector. This approach has the potential to significantly increase anti-arthritic drug concentration in joints without leading to systemic toxicity.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Drug Carriers; Female; Lipids; Male; Nanoparticles; Osteoarthritis; Rats

The paper considers the current pathogenesis, by choosing the actual targets of pharmacotherapy with available drugs. It reflects the cytokine mechanisms responsible for lesion of the synovial membranes, cartilage, and subchondral bone. Particular emphasis is laid on the role of chondroitin sulfate, glucosamine, vitamin D3 as drugs that affect the key components of pathogenesis, including the volume of resorptive cavities in the subchondral bone.

Topics: Bone Density; Bone Density Conservation Agents; Bone Resorption; Cholecalciferol; Chondroitin Sulfates; Cytokines; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

Osteoarthritis (OA) is the most common age-related rheumatic disease. Chondrocytes play a primary role in mediating cartilage destruction and extracellular matrix (ECM) breakdown, which are main features of the OA joint. Quantitative proteomics technologies are demonstrating a very interesting power for studying the molecular effects of some drugs currently used to treat OA patients, such as chondroitin sulfate (CS) and glucosamine (GlcN). In this work, we employed the iTRAQ (isobaric tags for relative and absolute quantitation) technique to assess the effect of CS and GlcN, both alone and in combination, in modifying cartilage ECM metabolism by the analysis of OA chondrocytes secretome. 186 different proteins secreted by the treated OA chondrocytes were identified. 36 of them presented statistically significant differences (p ≤ 0.05) between untreated and treated samples: 32 were increased and 4 decreased. The synergistic chondroprotective effect of CS and GlcN, firstly reported by our group at the intracellular level, is now demonstrated also at the extracellular level.

Topics: Aged; Aged, 80 and over; Cartilage, Articular; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Drug Synergism; Glucosamine; Humans; Osteoarthritis

Abstract Background: In intra-articular drug delivery, there are number of shortcomings such as lymphatic drainage from the synovial cavity, frequent dosing, adverse side effects and patient discomfort in the management of osteoarthritis (OA).. This research work reports the development and characterization of aceclofenac-loaded chondroitin sulfate (CS) conjugated (CS-SLN) and unconjugated solid lipid nanoparticles (SLN) for the effective management of OA.. The SLNs were prepared using modified solvent injection method and coupled with CS. They were further characterized for size and size distribution, zeta potential, surface morphology, % entrapment efficiency and in vitro drug release profile. Anti-inflammatory activity and in vivo performance was also predicted.. The particle size of the SLN and CS-SLN was found to be 143.4 ± 0.9 nm and 154.2 ± 1.1 nm, respectively. SLNs exhibited sustained drug release (SLN, 64.25 ± 0.75%; CS-SLN, 57.82 ± 0.62%) in vitro for more than 24 h. In vivo performance studies revealed the highest uptake of SLNs by the knee joint.. SLNs enhanced accumulation at the knee joint due to specific interactions with CD44, annexin and leptin receptors attributed to CS coupling.. CS-SLN could be potentially effective vector for the treatment or management of OA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Delayed-Action Preparations; Diclofenac; Drug Carriers; Humans; Injections, Intra-Articular; Lipids; Male; Nanoparticles; Osteoarthritis; Particle Size; Rats; Rats, Wistar; Technology, Pharmaceutical

Osteoarthritis is one of the most common, debilitating, musculoskeletal diseases; 12% associated with traumatic injury resulting in post-traumatic osteoarthritis (PTOA). Our objective was to develop a single impact model with cartilage "injury level" defined in terms of controlled combinations of strain rate to a maximum strain (both independent of cartilage load resistance) to study their sensitivity to articular cartilage cell viability and potential PTOA biomarkers. A servo-hydraulic test machine was used to measure canine humeral head cartilage explant thickness under repeatable pressure, then subject it (except sham and controls) to a single impact having controlled constant velocity V=1 or 100mm/s (strain rate 1.82 or 182/s) to maximum strain ε=10%, 30%, or 50%. Thereafter, explants were cultured in media for twelve days, with media changed at day 1, 2, 3, 6, 9, 12. Explant thickness was measured at day 0 (pre-injury), 6 and 12 (post-injury). Cell viability, and tissue collagen and glycosaminoglycan (GAG) were analyzed immediately post-injury and day 12. Culture media were tested for biomarkers: GAG, collagen II, chondroitin sulfate-846, nitric oxide, and prostaglandin E2 (PGE2). Detrimental effects on cell viability, and release of GAG and PGE2 to the media were primarily strain-dependent, (PGE2 being more prolonged and sensitive at lower strains). The cartilage injury model appears to be useful (possibly superior) for investigating the relationship between impact severity of injury and the onset of PTOA, specifically for discovery of biomarkers to evaluate the risk of developing clinical PTOA, and to compare effective treatments for arthritis prevention.

Topics: Animals; Biomarkers; Cartilage, Articular; Cell Survival; Chondroitin Sulfates; Collagen Type II; Dinoprostone; Dogs; Glycosaminoglycans; Humerus; Nitric Oxide; Osteoarthritis; Sprains and Strains; Stress, Mechanical

Erosive hand osteoarthritis is common and debilitating. Diagnosis is based on the presence of bone erosions which can appear late. Ultrasonography allows earlier diagnosis. The presence of apatite deposits could be of poor prognosis. Non pharmacological treatment includes the explanation of the inflammatory phenomena involved and the use of splints and physical therapy. Drug therapy includes analgesics, NSAIDs and infiltration of a steroid. Chondroitin sulfates have an analgesic and functional effect proven. DMARDs such as hydroxychloroquine and methotrexate have been used successfully. Some patients also benefited from isotope synoviortheses. New therapeutic ways, based on the pathophysiology of the disease, are new under evaluation.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Apatites; Chondroitin Sulfates; Glucocorticoids; Hand; Humans; Hydroxychloroquine; Methotrexate; Osteoarthritis; Prognosis

Aggrecan, a major macromolecule in cartilage, protects the extracellular matrix (ECM) from degradation during the progression of osteoarthritis (OA). However, aggrecan itself is also susceptible to proteolytic cleavage. Here, the use of a biomimetic proteoglycan (mAGC) is presented, which functionally mimics aggrecan but lacks the known cleavage sites, protecting the molecule from proteolytic degradation. The objective of this study is to test the efficacy of this molecule in ex vivo (human OA synovial fluid) and in vivo (Sprague-Dawley rats) osteoarthritic models. These results indicate that mAGC's may protect articular cartilage against the loss of key ECM components, and lower catabolic protein and gene expression in both models. This suppression of matrix degradation has the potential to provide a healthy environment for tissue repair.

Topics: Aged; Aged, 80 and over; Aggrecans; Animals; Biomimetic Materials; Cartilage, Articular; Cattle; Chondrocytes; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Extracellular Matrix; Gene Expression Regulation; Humans; Hyaluronic Acid; Inflammation Mediators; Matrix Metalloproteinase 13; Middle Aged; Osteoarthritis; Rats; Rats, Sprague-Dawley

Topics: Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Drug Therapy, Combination; Female; Glucosamine; Health Behavior; Humans; Middle Aged; Osteoarthritis

Topics: Arthritis; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis

The aim of this study was to investigate the correlations of severity of osteoarthritis (OA) and serum biomarkers including keratan sulfate (KS), hyaluronic acid (HA) and chondroitin sulfate (CS) 846 epitope. We also investigated the effect of glucosamine and fish collagen peptide (FCP) on OA. OA was induced in 12 rabbits (12 weeks of age) by anterior cruciate ligament transection (ACLT). After the surgery, the rabbits were orally administered FCP (F group), glucosamine (G group) or FCP and glucosamine (FG group) for 4 weeks. The control group was provided water ad libitum (C group). Blood was collected before surgery (pre-ACLT) and before euthanasia (post-ACLT) for serum marker measurement. Biomarker levels were measured by using commercial kits. We evaluated OA severity both macroscopically and histologically. Macroscopic evaluation showed mildly eroded condylar surfaces in the C group. Histological findings were significantly different from the FG and other groups. There were no significant differences between each group at post-ACLT in terms of serum KS, HA and CS 846. Histological assessment and serum biomarker measurements performed at post-ACLT showed a significant correlation between HA concentration and OA severity. Variations in the CS 846 concentration at pre-ACLT and post-ACLT were significantly correlated with OA severity. Administration of glucosamine and FCP had chondroprotective effects in the ACLT model. Serum biomarker concentrations were significantly correlated with cartilage injury. Serum biomarker measurement would be useful for monitoring articular cartilage damage in the clinical setting.

Topics: Animals; Anterior Cruciate Ligament; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Collagen; Disease Models, Animal; Glucosamine; Histocytochemistry; Hyaluronic Acid; Keratan Sulfate; Osteoarthritis; Rabbits; Statistics, Nonparametric

A novel selenium-chondroitin sulfate (SeCS) was synthesized by ultrasonic and dialysis method. With characterization by FTIR, XRD and TEM, the SeCS was found to form nanoparticles in distilled water through a self-aggregation progress. The SeCS nanoparticles had sizes between 30 and 200 nm with selenium entrapment efficiency of about 10.1%. The anti-toxin capacity of SeCS nanoparticles was demonstrated through MTT and apoptosis assays in vitro. Results indicated that the SeCS was less cytotoxic to chondrocytes than sodium selenite. In particular, the SeCS could obviously alleviate chondrocyte apoptosis induced by T-2 toxin compared to chondroitin sulfate. These results thus represent an advanced understanding of the properties of SeCS nanoparticles and demonstrate their exciting potential applications in therapy of Kashin-Beck disease (KBD) and osteoarthritis.

Topics: Apoptosis; Cell Line; Chondrocytes; Chondroitin Sulfates; Humans; Kashin-Beck Disease; Nanoparticles; Osteoarthritis; Selenium

Our objectives were to characterize the urinary excretion of glycosaminoglycans (GAGs) in horse osteoarthritis, and to investigate the effects of chondroitin sulfate (CS) and glucosamine (GlcN) upon the disease. Urinary GAGs were measured in 47 athletic horses, 20 healthy and 27 with osteoarthritis. The effects of CS and GlcN were investigated in mild osteoarthritis. In comparison to normal, urinary GAGs were increased in osteoarthritis, including mild osteoarthritis affecting only one joint. Treatment with CS+GlcN led to a long lasting increase in the urinary CS and keratan sulfate (KS), and significant improvement in flexion test of tarsocrural and metacarpophalangeal joints was observed. In conclusion, urinary CS and KS seems to reflect the turnover rates of cartilage matrix proteoglycans, and the measurement of these compounds could provide objective means of evaluating and monitoring joint diseases.

Topics: Animals; Anti-Inflammatory Agents; Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Glycosaminoglycans; Horse Diseases; Horses; Osteoarthritis

Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs.

Topics: Animals; Apoptosis; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Glucosamine; Guinea Pigs; Matrix Metalloproteinase 3; Osteoarthritis; RNA, Messenger; Up-Regulation

Articular cartilage undergoes severe loss of proteoglycan and its constituent glycosaminoglycans (GAGs) in osteoarthritis. We hypothesize that the low GAG content of osteoarthritic cartilage renders the tissue susceptible to pathological vascularization. This was investigated using an in vitro angiogenesis model assessing endothelial cell adhesion to GAG-depleted cartilage explants. Bovine cartilage explants were treated with hyaluronidase to deplete GAG content and then seeded with fluorescently tagged human endothelial cells (HMEC-1). HMEC-1 adherence was assessed after 4 hr and 7 days. The effect of hyaluronidase treatment on GAG content, chondrocyte viability, and biochemical composition of the extracellular matrix was also determined. Hyaluronidase treatment reduced the GAG content of cartilage explants by 78 ± 3% compared with that of controls (p < 0.0001). GAG depletion was associated with significantly more HMEC-1 adherence on both the surface (superficial zone) and the underside (deep zone) of the explants (both p < 0.0001). The latter provided a more favorable environment for extended culture of HMEC-1 compared with the articulating surface. Hyaluronidase treatment altered the immunostaining for chondroitin sulfate epitopes, but not for lubricin. Our results support the hypothesis that articular cartilage GAGs are antiadhesive to endothelial cells and suggest that chondroitin sulfate and/or hyaluronan are responsible. The loss of these GAGs in osteoarthritis may allow osteochondral angiogenesis resulting in disease progression.

Topics: Animals; Cartilage, Articular; Cattle; Cell Adhesion; Cell Survival; Chondrocytes; Chondroitin Sulfates; Disease Progression; Epitopes; Female; Glycoproteins; Glycosaminoglycans; Human Umbilical Vein Endothelial Cells; Humans; Hyaluronoglucosaminidase; Neovascularization, Physiologic; Organ Culture Techniques; Osteoarthritis

Chondroitin sulfate (CS) is a symptomatic slow acting drug for osteoarthritis (OA) widely used for the treatment of this highly prevalent disease, characterized by articular cartilage degradation. However, little is known about its mechanism of action, and recent large scale clinical trials have reported variable results on OA symptoms. Herein, we aimed to study the modulations in the intracellular proteome and the secretome of human articular cartilage cells (chondrocytes) treated with three different CS compounds, with different origin or purity, by two complementary proteomic approaches. Osteoarthritic cells were treated with 200 μg/ml of each brand of CS. Quantitative proteomics experiments were carried out by the DIGE and stable isotope labeling with amino acids in cell culture (SILAC) techniques, followed by LC-MALDI-MS/MS analysis. The DIGE study, carried out on chondrocyte whole cell extracts, led to the detection of 46 spots that were differential between conditions in our study: 27 were modulated by CS1, 4 were modulated by CS2, and 15 were modulated by CS3. The SILAC experiment, carried out on the subset of chondrocyte-secreted proteins, allowed us to identify 104 different proteins. Most of them were extracellular matrix components, and 21 were modulated by CS1, 13 were modulated by CS2, and 9 were modulated by CS3. Each of the studied compounds induces a characteristic protein profile in OA chondrocytes. CS1 displayed the widest effect but increased the mitochondrial superoxide dismutase, the cartilage oligomeric matrix protein, and some catabolic or inflammatory factors like interstitial collagenase, stromelysin-1, and pentraxin-related protein. CS2 and CS3, on the other hand, increased a number of structural proteins, growth factors, and extracellular matrix proteins. Our study shows how, from the three CS compounds tested, CS1 induces the activation of inflammatory and catabolic pathways, whereas CS2 and CS3 induce an anti-inflammatory and anabolic response. The data presented emphasize the importance of employing high quality CS compounds, supported by controlled clinical trials, in the therapy of OA. Finally, the present work exemplifies the usefulness of proteomic approaches in pharmacological studies.

Topics: Amino Acid Sequence; Cell Extracts; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Extracellular Matrix Proteins; Humans; Intracellular Fluid; Molecular Sequence Data; Osteoarthritis; Peptide Fragments; Proteome; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Two-Dimensional Difference Gel Electrophoresis

This review emphasizes the importance of glycobiology in nature and aims to highlight, simplify and summarize the multiple functions and structural complexities of the different oligosaccharide combinatorial domains that are found in chondroitin sulphate/dermatan sulphate (CS/DS) glycosaminoglycan (GAG) chains. For example, there are 1008 different pentasaccharide sequences possible within CS, DS or CS/DS hybrid GAG chains. These combinatorial possibilities provide numerous potential ligand-binding domains that are important for cell and extracellular matrix interactions as well as specific associations with cytokines, chemokines, morphogens and growth factors that regulate cellular differentiation and proliferation during tissue development, for example, morphogen gradient establishment. The review provides some details of the large and diverse number of different enzymes that are involved in CS/DS biosynthesis and attempts to explain how differences in their expression patterns in different cell types can lead to subtle but important differences in the GAG metabolism that influence cellular proliferation and differentiation in development as well as regeneration and repair in disease. Our laboratory was the first to generate and characterize monoclonal antibodies (mAb) that very specifically recognize different ‘native’ sulphation motif/epitopes in CS/DS GAG chains. These monoclonal antibodies have been used to identify very specific spatio-temporal expression patterns of CS/DS sulphation motifs that occur during tissue and organ development (in particular their association with stem/progenitor cell niches) and also their recapitulated expression in adult tissues with the onset of degenerative joint diseases. In summary, diversity in CS/DS sulphation motif expression is a very important necessity for animal life as we know it.

Topics: Animals; Antibodies, Monoclonal; Chondroitin Sulfates; Dermatan Sulfate; Epitopes; Humans; Osteoarthritis

A simple and accurate capillary electrophoresis (CE) method was developed to simultaneously separate and quantify heparin, chondroitin sulfate and hyaluronic acid. The relative standard deviations (intra-day) of migration time, peak height and peak area for heparin, chondroitin sulfate and hyaluronic acid were lower than 1.11, 5.45 and 2.82%, respectively. The limits of detection of heparin, chondroitin sulfate and hyaluronic acid were 0.91, 0.12 and 9.04 × 10(-3) mg/mL, respectively. The developed electrophoretic method was successfully applied to the analysis of commercial drug products and biological samples containing chondroitin sulfate and/or hyaluronic acid. The recoveries for chondroitin sulfate and hyaluronic acid were in the range of 95.9 ~107.0%. This was the first time the content of hyaluronic acid in the synovial fluids from osteoarthritic rabbits was investigated by CE. The results suggested that hyaluronic acid in the synovial fluids from osteoarthritic rabbits may be further metabolized and the administration of chondroitin sulfate or hyaluronic acid could affect the content and metabolism of hyaluronic acid in the synovial fluids. The developed CE method was simple to implement without sample pretreatment such as depolymerisation, very repeatable and easily transferred from lab to lab.

Topics: Animals; Chondroitin Sulfates; Electrophoresis, Capillary; Heparin; Hyaluronic Acid; Limit of Detection; Osteoarthritis; Pharmaceutical Preparations; Rabbits; Synovial Fluid

This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1β and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied.. Biopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria, including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. We assessed the expression of CD45, von Willebrand factor and vascular endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or I synovial cells was quantified by ELISA. SFC were cultured in the absence or in the presence of IL-1β (1 ng/ml) and with or without CS (10, 50, 200 μg/ml). Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production of VEGI and TSP-1 was also estimated by ELISA.. Immunohistochemistry showed the increase of lymphocyte infiltration, vascular density and VEGF expression in I compared to N/R synovial biopsies. Synovial cells from I areas produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R synovial biopsies. The expression of pro-angiogenic factors by SFC was stimulated by IL-1β. A time dependent regulation of the expression of anti-angiogenic factor genes was observed. IL-1β stimulated the expression of anti-angiogenic factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL-1β on anti-angiogenic factors, VEGI and TSP-1.. We demonstrated that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL-1β induced an imbalance between pro- and anti-angiogenic factors in SFC and CS tended to normalize this IL-1β-induced imbalance, providing a new possible mechanism of action of this drug.

Topics: Aged; Aged, 80 and over; Cells, Cultured; Chondroitin Sulfates; Female; Humans; Male; Middle Aged; Neovascularization, Pathologic; Osteoarthritis; Synovial Membrane

Osteoarthritis (OA) is one of the major causes of pain and of outpatient's clinics. 15 years ago, physiopathology of OA and its potential therapeutic targets were announced to be better understood, but the results of therapeutic trials were finally not as convincing as expected. Slow Acting Drugs (SADs) are part of the treatments evaluated in OA. Even if evidence based medicine is low, positive effects of SADs have been observed. We can reasonably propose these treatments for a short test period. It can sometimes enable us to decrease the dosage of others treatment such as NSAIDs. In any case, the physician must properly inform the patient about products available in Switzerland and must be aware of degrees of purity and costs of the products available on the intemet.

Topics: Antirheumatic Agents; Chondroitin Sulfates; Delayed-Action Preparations; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Hyaluronic Acid; Osteoarthritis; Pain; Treatment Outcome; Viscosupplements

Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS1 region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA.

Topics: ADAM Proteins; ADAMTS4 Protein; Adolescent; Adult; Aged; Aged, 80 and over; Aggrecans; Cartilage, Articular; Chondroitin Sulfates; Extracellular Matrix; Humans; Keratan Sulfate; Knee Injuries; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Middle Aged; Osteoarthritis; Peptide Fragments; Procollagen N-Endopeptidase; Protein Interaction Domains and Motifs; Proteolysis; Recombinant Proteins; Substrate Specificity; Synovial Fluid; Young Adult

Topics: Beverages; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Glucosamine; Humans; Joints; Osteoarthritis; United States

Topics: Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Severity of Illness Index; Treatment Outcome

The relative contribution of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5 to aggrecan degradation under oncostatin M (OSM) stimulation, the role of the ancillary domains of the aggrecanases on their ability to cleave within the chondroitin sulfate (CS)-2 region, the role of hyaluronidases (HYAL) in stimulating aggrecan release in the absence of proteolysis, and the identity of the hyaluronidase involved in OSM-mediated cartilage breakdown were investigated. Bovine articular cartilage explants were cultured in the presence of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and/or OSM, or treated with trypsin and/or hyaluronidase. Aggrecan was digested with various domain-truncated isoforms of ADAMTS4 and ADAMTS5. Aggrecan and link protein degradation and release were analyzed by immunoblotting. Aggrecanase and HYAL gene expression were determined. ADAMTS4 was the most inducible aggrecanase upon cytokine stimulation, whereas ADAMTS5 was the most abundant aggrecanase. ADAMTS5 was the most active aggrecanase and was responsible for the generation of an OSM-specific degradation pattern in the CS-2 region. Its ability to cleave at the OSM-specific site adjacent to the aggrecan G3 region was enhanced by truncation of the C-terminal thrombospondin domain, but reduced by further truncation of both the spacer and cysteine-rich domains of the enzyme. OSM has the ability to mediate proteoglycan release through hyaluronan degradation, under conditions where HYAL-2 is the predominant hyaluronidase being expressed. Compared to other catabolic cytokines, OSM exhibits a unique potential at degrading the proteoglycan aggregate, by promoting early robust aggrecanolysis, primarily through the action of ADAMTS5, and hyaluronan degradation.

Topics: ADAM Proteins; Aggrecans; Animals; Cartilage, Articular; Cattle; Cells, Cultured; Chondroitin Sulfates; Cytokines; Electrophoresis, Polyacrylamide Gel; Hyaluronoglucosaminidase; Immunoblotting; Interleukin-1beta; Metalloproteases; Oncostatin M; Osteoarthritis; Protein Isoforms; Thrombospondins; Tissue Culture Techniques; Trypsin; Tumor Necrosis Factor-alpha

The purpose of the study was to design and develop unique drug delivery systems with controllable multiple burst releases of drugs for treating osteoarthritis. Chondroitin sulfate (CS) was encapsulated into four types of PLGA materials, that is, PLGA 50:50, PLGA 65:35, PLGA 75:25, and PLGA 85:15. The effects of microsphere size and various combinations of blend PLGA microspheres on CS release were investigated. The cytotoxicity of the CS-encapsulated microspheres was investigated according to the ISO 10993 guideline. Our study showed that the encapsulation efficiency of CS into PLGA 50:50 microspheres varied with the size of microspheres; however, the encapsulation efficiencies of CS into PLGA microspheres were independent of the types of PLGA materials. The size of PLGA microspheres was shown to affect the rate of CS release. With the increase of microsphere size from 75-150 μm to 300-355 μm, the initial CS release decreased. Further increase in microsphere size led to an increase in the initial CS release. In addition, combination of different types of PLGA microspheres was shown to be capable of achieving multiple burst CS releases. Moreover, the CS encapsulated PLGA microspheres were shown to be non-cytotoxic. This study proved the concept of multiple burst drug releases that were achieved by encapsulating CS into different types of PLGA microspheres and delivering CS from systems consisting of mixed types of PLGA microspheres, which may be applied to treat osteoarthritis by mimicking multiple intra-joint injection of therapeutic agents.

Topics: Biocompatible Materials; Chondroitin Sulfates; Drug Compounding; Drug Delivery Systems; Humans; Lactic Acid; Materials Testing; Microscopy, Electron, Scanning; Microspheres; Osteoarthritis; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer

Topics: Chondroitin Sulfates; Escherichia coli; Nuclear Magnetic Resonance, Biomolecular; Osteoarthritis

Chondroitin sulfate (CS) has an important role in cell division, in the central nervous system, and in joint-related pathologies such as osteoarthritis. Due to the complex chemical structure and biological importance of CS, simple, sensitive, high resolution, and robust analytical methods are needed for the analysis of CS disaccharides and oligosaccharides. An ion-pairing, reversed-phase, ultraperformance liquid chromatography (IPRP-UPLC) separation, coupled to electrospray ionization mass spectrometry with an ion trap mass analyzer, was applied for the analyses of CS-derived disaccharides. UPLC separation technology uses small particle diameter, short column length, and elevated column temperature to obtain high resolution and sensitivity. Hexylamine (15 mM) was selected as the optimal ion-pairing reagent.

Topics: Amines; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disaccharides; Osteoarthritis; Propanols; Spectrometry, Mass, Electrospray Ionization

Chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) are present in high levels in connective tissue where they play roles as structural molecules and in protein-binding interactions. Recent developments in the techniques for analysis of CS/DS using capillary electrophoresis (CE) have enabled progress in the understanding of changes in CS/DS structure that accompany connective tissue diseases including osteoarthritis. Key to these developments is the ability to extract CS/DS GAGs from small quantities of connective tissue. This chapter describes a method for connective tissue GAG extraction, derivatization, and workup for subsequent capillary electrophoretic and/or mass spectrometric analysis.

Topics: Adult; Child; Chondroitin; Chondroitin Sulfates; Chromatography, Ion Exchange; Connective Tissue; Dermatan Sulfate; Electrophoresis, Capillary; Humans; Mass Spectrometry; Molecular Biology; Oligosaccharides; Osteoarthritis

As part of the National Institutes of Health (NIH)-sponsored Glucosamine/Chondroitin sulfate Arthritis Intervention Trial (GAIT) our objective here was to examine (1) the pharmacokinetics (PK) of glucosamine (GlcN) and chondroitin sulfate (CS) when taken separately or in combination as a single dose in normal individuals (n=29) and (2) the PK of GlcN and CS when taken as a single dose after 3 months daily dosing with GlcN, CS or GlcN+CS, in patients with symptomatic knee pain (n=28).. The concentration of GlcN in the circulation was determined by established fluorophore-assisted carbohydrate electrophoresis (FACE) methods. The hydrodynamic size and disaccharide composition of CS chains in the circulation and dosage samples was determined by Superose 6 chromatography and FACE.. We show that circulating levels of CS in human plasma are about 20 microg/ml. Most significantly, the endogenous concentration and CS disaccharide composition were not detectably altered by ingestion of CS, when the CS was taken alone or in combination with GlcN. On the other hand, the Cmax (single-dose study) and AUC values (multiple-dose study) for ingested GlcN were significantly reduced by combination dosing with CS, relative to GlcN dosing alone.. We conclude that pain relief perceived following ingestion of CS probably does not depend on simultaneous or prior intake of GlcN. Further, such effects on joint pain, if present, probably do not result from ingested CS reaching the joint space but may result from changes in cellular activities in the gut lining or in the liver, where concentrations of ingested CS, or its breakdown products, could be substantially elevated following oral ingestion. Moreover, since combined dosing of GlcN with CS was found to reduce the plasma levels seen with GlcN dosing alone, any improved pain relief by combination dosing cannot be explained by higher circulating concentrations of GlcN.

Topics: Administration, Oral; Adult; Arthralgia; Chondroitin Sulfates; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Pain Measurement; Treatment Outcome; Young Adult

To clarify the exact anti-arthritic action mechanisms of chondroitin sulfate (CS), we evaluated the effects of CS derived from shark cartilage (CS-SC) composed mainly of chondroitin-6-sulfate and porcine trachea cartilage (CS-PC) composed mostly of chondrotin-4-sulfate on the functions of human articular chondrocytes and synovial fibroblasts. Both CS-SC and CS-PC (from 1 to 100 mug/ml) effectively suppressed the interleukin (IL)-1beta (10 ng/ml)-enhanced gene expression of aggrecanase-1/a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 in articular chondrocytes embedded in alginate beads and synovial fibroblasts. In addition, CS-SC and CS-PC overcame the IL-1beta-mediated suppression of the aggrecan core protein mRNA, and suppressed the IL-1beta-enhanced collagenase-3/matrix metalloproteinase (MMP)-13 gene expression in chondrocytes. CS-PC, but not CS-SC effectively recovered the IL-1beta-reduced gene expression of tissue inhibitor of metalloproteinases (TIMP)-3 in chondrocytes, and enhanced the production of TIMP-1 in synovial fibroblasts. It is noteworthy that CS is able to modulate the function of synovial fibroblasts as well as that of chondrocytes. Therefore, CS is very likely to be multifunctional chondroprotective material for degenerative arthritic diseases.

Topics: ADAM Proteins; Animals; Cartilage; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Fibroblasts; Gene Expression; Humans; Interleukin-1beta; Matrix Metalloproteinase 13; Osteoarthritis; Protective Agents; RNA, Messenger; Sharks; Swine; Synovial Membrane; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-3

Mesenchymal stem cells (MSCs) have the potential to differentiate into distinct mesenchymal tissues; including cartilage and bone, they can be an attractive cell source for cartilage tissue engineering approaches. Our objective here was to compare the in vitro chondrogenic potential of MSCs isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) with cells from normal donors.. Marrow samples were removed during bone surgery and adherent cell cultures were established. The cells were then passed into a newly developed microaggregate culture system in a medium containing transforming growth factor beta3, insulin, dexamethasone and/or demineralized bone matrix. In vitro chondrogenic activity was measured as metabolic sulfate incorporation and type II collagen expression in pellet cultures.. Culture-expanded MSCs from RA and OA patients did not differ significantly from the normal population with respect to their chondrogenic potential in vitro. Capability of total protein and proteoglycan synthesis as well as collagen II mRNA expression by cell aggregates was similar for all cell preparations in the presence of the appropriate growth and differentiation factors. Chondroprotective drugs such as chondroitin sulfate and glucosamine enhanced, whereas chloroquine inhibited chondrogenesis in normal donor-derived or patient-derived MSC cultures. Galectin-1, a beta-galactoside-binding protein with marked anti-inflammatory activity, stimulated the chondrogenic differentiation of mesenchymal cells in low (<2 microg/ml) concentration.. These findings show that MSCs from RA and OA patients possess similar chondrogenic potential as MSCs isolated from healthy donors, therefore these cells may serve as a potential new prospect in cartilage replacement therapy.

Topics: Adipogenesis; Aged; Arthritis, Rheumatoid; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Chondrogenesis; Chondroitin Sulfates; Collagen Type II; Female; Galectins; Glucosamine; Humans; Male; Mesenchymal Stem Cells; Microscopy, Electron, Transmission; Middle Aged; Osteoarthritis; Osteogenesis; Reverse Transcriptase Polymerase Chain Reaction

Topics: Cartilage, Articular; Chondroitin Sulfates; Humans; Injections, Intra-Articular; Osteoarthritis

Dynamics of clinical parameters and quality of life (QL) was evaluated in 281 patients with knee and hip osteoarthrosis (OA) during long-term treatment of different duration. The group was dominated by women (71%) aged 41-65 yr with grade I-III OA according to Kellgren. Patients of groups I and II received only non-steroidal anti-inflammatory drugs (diclofenac, nize), those of groups III-IV the same drugs in combination with structum, chondrolon, and zeel T respectively. Clinical parameters were assessed based on VAS at rest and in motion, Leken's indices, and WOMAC, QL from SF-36 questionnaire. Variable clinical course was recorded in patients treated with non-steroidal drugs alone that caused rapid improvement after the very first treatment sessions followed by deterioration of the patients' condition. Addition of structum resulted in marked optimization of clinical and QL parameters within 3 months after the onset of combined therapy. Similar effect was obtained using chondrolon and zeel T, but 2-3 clinical parameters and 3 QL parameters were not significantly different from the initial ones after 12 and 24 months of therapy. It is concluded that structum produced the best therapeutic effect followed by chondrolon and zeel T. Non-steroidal anti-inflammatory drugs had no beneficial action whatever in patients with OA.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Diclofenac; Female; Humans; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Quality of Life; Radiography; Surveys and Questionnaires

The objective of this research work is to prepare a new and reliable radiopharmaceutical for osteoarthral cartilage imaging. Chondroitin sulfate (CS) was labeled directly with 99mTc by "pretinning" method, the labeling efficiency was 79.30% +/- 1.72% and radiochemical purity was 90.12% +/- 1l.23% after filtration by use of asepsis filter membrane. The biodistribution of 99Tc-CS was studied at 10, 30 min and 1, 2, 3, 4, 5, 6, 7, 8, 9 h respectively after caudal vein injection in normal mice,which showed that the radiolabeled product was washed out from blood quickly, and it was mainly excreted through kidney, but 99mTc-CS had distinctive characteristic of philo- cartilage. Scintigraphy of 99mTc-CS was performed on the rabbit with ostarthritis at 5 h after intravenous injection; the scintigram was clear,and the focus showed increased radiopharmaceutical uptake. The radioactivity ratio of the injured/uninjured side (T/NT) calculated over the region of interest (ROI) was 3.0 +/- 0.6 (P < 0.05). These results indicate that 99mTc-CS is an easily prepared compound with the characteristic of high philo-cartilage and it may be a new ideal cartilage imaging agent.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Female; Male; Mice; Mice, Inbred BALB C; Organotechnetium Compounds; Osteoarthritis; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Random Allocation

We have examined the occurrence of the inflammation-associated inter-alpha-trypsin inhibitor (IalphaI) components, bikunin, heavy chain (HC)1 and HC2 in normal cartilage and osteoarthritis (OA) cartilage and synovial fluids.. Cartilage extracts from normal donors and late-stage OA patients, and synovial fluids from OA patients were studied by Western blot with multiple antibodies to bikunin, HC1 and HC2. Cell and matrix localization was determined by immunohistochemistry and mRNA by RT-PCR.. Bikunin.chondroitin sulfate (CS) and IalphaI were abundant in OA cartilages, but virtually undetectable in normal. In both OA and normal cartilages, HCs were largely present in a novel C-terminally truncated 50-kDa form, with most, if not all of these being attached to CS on a proteoglycan other than bikunin. Synovial fluids from OA patients contained bikunin.CS and full-length (approximately 90 kDa) HCs linked to hyaluronan (HA) as HC.HA (SHAP.HA). Immunohistochemistry showed intracellular and cell-associated staining for bikunin and HCs, consistent with their synthesis by superficial zone chondrocytes. PCR on multiple human normal and OA cartilage samples detected transcripts for HC1 and HC2 but not for bikunin. In OA cartilages, immunostaining was predominantly matrix-associated, being most intense in regions with a pannus-like fibrotic overgrowth.. The truncated structure of HCs, their attachment to a proteoglycan other than bikunin, PCR data and intracellular staining are all consistent with synthesis of HC1 and HC2 by human articular chondrocytes. The presence of bikunin.CS and IalphaI in OA cartilage, but not in normal, appears to be due to diffusional uptake and retention through fibrillated (but not deeply fissured) cartilage surfaces.

Topics: Alpha-Globulins; Blotting, Western; Cartilage, Articular; Chondrocytes; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Humans; Hyaluronic Acid; Osteoarthritis; Proteoglycans; Reverse Transcriptase Polymerase Chain Reaction; Synovial Fluid

To observe the effect of glucosamine (GS) and chondroitin sulfate (CS) on histopathological, histochemical features of articular cartilage and on the aggrecan serum level in Hartley guinea pigs: a kind of primary OA animal model.. 120 female Hartley guinea pigs aged 2 months were randomly divided into 3 test groups and a control group, 30 animals for each group. The three test groups refer to GS group, CS group and combined group. GS group has been administrated with 1 g/kg bw GS, CS group administrated with 0.5 g/kg bw CS, combined group with 1 g/kg bw GS + 0.5 g/kg bw CS and a control group administrated with distilled water. The above four substances were treated via ad limbitum for a period of 5 months. Before dosing and after each monthly treatment during the five months, knee joints Cartilage specimens from 5 guinea pigs each group were examined through histopathological method (H. E stain) and histopathological method (Alcain Blue, PAS and Mallory stain), and the serum levels of aggrecan were detected synchronously.. During the entire 5 months period, distinct pathological lesions appeared just after the first month in control group. And the distinct pathological lesions didn't appear until the third month ended in GS group. In CS group, moderate pathological lesions were observed in the fourth month, while there were almost no obviously pathological changes in combined group during the whole test period. The serum levels of aggrecan in all three test groups were all decreased slower after 4 months treatment than those in the control group, with a significant difference (P < 0.05).. GS and CS can postpone and inhibit the pathological changes of articular cartilage, as well as serum aggrecan levels decrease in Hartley guinea pigs. The effect of GS and CS used in combination was stronger than individual GS and CS, showing a repair property.

Topics: Aggrecans; Animals; Cartilage, Articular; Chondroitin Sulfates; Female; Glucosamine; Guinea Pigs; Osteoarthritis

Osteoarthritis is primarily characterized by areas of destruction of articular cartilage and by synovitis. Articular damage and synovitis are secondary to local increase of pro-inflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha), enzymes with proteolytic activity (matrix metalloproteinases), and enzymes with pro-inflammatory activity (cyclooxygenase-2 and nitric oxide synthase-2). Enhanced expression of these proteins in chondrocytes and in synovial membrane appears associated to the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB). Chondroitin sulfate (CS) prevents joint space narrowing and reduces joint swelling and effusion. To produce these effects, CS elicits an anti-inflammatory effect at the chondral and synovial levels. CS and its disaccharides reduce NF-kappaB nuclear translocation, probably by diminishing extracellular signal-regulated kinase1/2, p38mitogen-activated protein kinase and c-Jun N-terminal kinase activation. This review discusses the evidence supporting that CS pleiotropic effects in chondrocytes and synoviocytes are primarily due to a common mechanism, e.g., the inhibition of NF-kappaB nuclear translocation.

Topics: Animals; Anti-Inflammatory Agents; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Dogs; Humans; Interleukin-1; Matrix Metalloproteinases; NF-kappa B; Osteoarthritis; Randomized Controlled Trials as Topic; Synovitis; Tumor Necrosis Factor-alpha

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 +/- 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 +/- 100.05 ng/ml) was significantly lower than that in the non-HD group (136 +/- 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 +/- 59.71 ng/ml) was lower than that in the non HD group (245.45 +/- 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.

Topics: Animals; Biomarkers; Body Weight; Chondroitin Sulfates; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Hip Dysplasia, Canine; Hyaluronic Acid; Male; Osteoarthritis; Prevalence; Sex Characteristics

Topics: Acetates; Antirheumatic Agents; Arthritis, Rheumatoid; Chondroitin Sulfates; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Osteoarthritis; Piperidines; Pyrimidines; Pyrroles

Topics: Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis

Early in the pathological process of osteoarthritis (OA), subchondral bone remodelling, which is related to altered osteoblast metabolism, takes place. In the present study, we explored in human OA subchondral bone whether chondroitin sulfate (CS), glucosamine sulfate (GS), or both together affect the major bone biomarkers, osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), and the pro-resorptive activity of OA osteoblasts. The effect of CS (200 mug/mL), GS (50 and 200 mug/mL), or both together on human OA subchondral bone osteoblasts, in the presence or absence of 1,25(OH)2D3 (vitamin D3) (50 nM), was determined on the bone biomarkers alkaline phosphatase and osteocalcin, on the expression (mRNA) and production (enzyme-linked immunosorbent assay) of bone remodelling factors OPG and RANKL, and on the pro-resorptive activity of these cells. For the latter experiments, human OA osteoblasts were incubated with differentiated peripheral blood mononuclear cells on a sub-micron synthetic calcium phosphate thin film. Data showed that CS and GS affected neither basal nor vitamin D3-induced alkaline phosphatase or osteocalcin release. Interestingly, OPG expression and production under basal conditions or vitamin D3 treatment were upregulated by CS and by both CS and GS incubated together. Under basal conditions, RANKL expression was significantly reduced by CS and by both drugs incubated together. Under vitamin D3, these drugs also showed a decrease in RANKL level, which, however, did not reach statistical significance. Importantly, under basal conditions, CS and both compounds combined significantly upregulated the expression ratio of OPG/RANKL. Vitamin D3 decreased this ratio, and GS further decreased it. Both drugs reduced the resorption activity, and statistical significance was reached for GS and when CS and GS were incubated together. Our data indicate that CS and GS do not overly affect cell integrity or bone biomarkers. Yet CS and both compounds together increase the expression ratio of OPG/RANKL, suggesting a positive effect on OA subchondral bone structural changes. This was confirmed by the decreased resorptive activity for the combination of CS and GS. These data are of major significance and may help to explain how these two drugs exert a positive effect on OA pathophysiology.

Topics: Aged; Alkaline Phosphatase; Base Sequence; Biomarkers; Bone Resorption; Calcitriol; Cells, Cultured; Chondroitin Sulfates; DNA Primers; Drug Synergism; Glucosamine; Humans; Middle Aged; Osteoarthritis; Osteoblasts; Osteocalcin; Osteoprotegerin; RANK Ligand; RNA, Messenger

Serum hyaluronan (HA) and chondroitin sulfate (CS) epitopes WF6 and 3B3 (+) were determined to investigate disease association in patients with osteoarthritis (OA), rheumatoid arthritis (RA) and healthy controls.. Specific assays for HA and CS epitopes WF6 and 3B3 (+) were established and applied to a cross-sectional study of serum samples from patients (96 OA, 57 RA and 50 healthy controls).. Both CS epitopes were increased in serum of many OA and RA patients and average levels were significantly above in healthy controls. In contrast serum HA was increased in RA, but only in few OA patients.. CS epitopes WF6 and 3B3 (+) are raised in serum of patients with both OA and RA and were thus distinct from serum HA. The results suggest that OA may be detected systemically as well as RA. The range of levels of CS epitopes detected in OA and RA was wide and correlation with any aspect of disease activity is yet to be determined.

Topics: Adult; Aged; Antibodies, Monoclonal; Arthritis, Rheumatoid; Biomarkers; Chondroitin Sulfates; Cross-Sectional Studies; Epitopes; Female; Humans; Hyaluronic Acid; Male; Middle Aged; Osteoarthritis

Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Glucosamine; Humans; Osteoarthritis; Pain; Pyrazoles; Sulfonamides; Treatment Outcome

Earlier studies with glucosamines in patients with osteoarthritis have shown conflicting results. A placebo-controlled randomised trial was now carried out in 1583 patients with osteoarthritis. The primary endpoint was a 20% reduction in knee pain between baseline and week 24 according to the 'Western Ontario and McMaster Universities arthritis index'(WOMAC)-score. No statistically significant difference was found between the groups using placebo (60% response), glucosamine (64%), chondroitin sulphate (65%) or combination therapy (67%). The results of this trial do not support the hypothesis that glucosamines have a positive effect on symptoms in patients with osteoarthritis of the knee. However, (a) the chance of a statistically significant difference decreases with increasing magnitude of the placebo response, (b) there was a statistically significant reduction in the patients with moderate to severe pain, (c) when the pain was assessed with the more sensitive 'Outcome measures in rheumatology clinical trials'(OMERACT)-'Osteoarthritis Research Society International'(OARSI)-score, there was a better response in the group given combined treatment, (d) the data on radiological progression and the effects on cartilage markers must still come in, and (e) the efficacy may have been higher ifa different dietary supplement had been used. These questions on the design and the robustness of the study indicate that further studies are necessary.

Topics: Chondroitin Sulfates; Dietary Supplements; Drug Therapy, Combination; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Arthralgia; Chondroitin Sulfates; Clinical Trials as Topic; Dietary Supplements; Glucosamine; Humans; Osteoarthritis; Placebo Effect; Treatment Outcome

Topics: Chondroitin Sulfates; Dietary Supplements; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Treatment Outcome

The aim of this study was to evaluate histologically the action of chondroitin sulphate in osteoarthritis experimentally induced by continuous immobilization. Fourteen young female Norfolk rabbits aged 2.5-3 months at the beginning of the experiment were divided into two equitable groups submitted to immobilization of the right knee for a period of 12 weeks. The treated group received 1.0 ml/animal/s.c. of 12% chondroitin sulphate, once a week for 12 weeks, and the untreated group did not receive any treatment. Two additional animals were not submitted to knee immobilization (sham group). Microscopical examination of knee preparations stained with haematoxylin-eosin and Masson trichrome showed lesions of both joints in treated and untreated groups, with no significant difference between the scores obtained for the right and left knees. Examination of preparations stained with picrosirius red showed collagen fibre alignment and misalignment in the right and left knees of the animals of all groups, but statistic analysis could not be performed. It was not possible to differentiate the proteoglycan concentration between limbs or groups (treated and untreated) by safranin O or toluidine blue staining. It was possible to conclude that the chondroitin sulphate was not able to reduce the histological changes induced by this osteoarthritis experimental model.

Topics: Animals; Chondroitin Sulfates; Disease Models, Animal; Female; Immobilization; Knee Joint; Osteoarthritis; Rabbits; Treatment Outcome

Topics: Chondroitin Sulfates; Finger Joint; Humans; Long-Term Care; Osteoarthritis; Treatment Outcome

In order to assess agent with modulating properties of the course of the arthrosic condition, the so-called SYSADOA (Symptomatic Slow Acting Drugs for Osteoarthritis) and "structure modifiers" have been defined. Glucosamine sulfate, chrondroitin sulfate and diacerein have been considered among these agents. Based on the published data and according to the evidence available, the SYSADOA have symptomatic effects and can modify the structure. However, although there is scientific evidence for the use of these drugs in arthrosis treatment, the limited intensity of their action over the placebo makes it necessary to evaluate the clinical relevance of their application before recommending their generalized use.

Topics: Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

Clinical trials in human and veterinary literature have documented the benefits of oral nutraceutical joint supplements containing glucosamine (GU) and chondroitin sulphate (CS) to treat mild to moderate osteoarthritis, but the effects of these components have not yet been conclusively determined.. To assess varying dosages of GU and CS on normal and interleukin-1alpha (IL-1) conditioned equine cartilage explants and rationalise the use of these products.. Treatment would not be detrimental to cartilage metabolism and higher dosages and the combination of GU and CS would be more beneficial than lower dosages and. GU or CS alone.. Articular cartilage explants collected from the femoral trochlea and condyles were cultured in normal and IL-1 conditioned media. Treatment groups included 0, 12.5, 25,125 and 250 microg/ml concentrations of GU alone, CS alone, or GU+CS in combination. Glycosaminoglycan (GAG) synthesis and total GAG content in the explants and media were analysed.. There were no detrimental effects of GU, CS or GU+CS on cartilage metabolism. High dosages of GU+CS reduced total GAG release into the media (degradation).. Our results suggests that GU+CS may prevent cartilage GAG degradation.. The combination of GU and CS may be more effective in preventing or treating osteoarthritis in horses than either product alone.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Culture Media; Dose-Response Relationship, Drug; Drug Synergism; Glucosamine; Glycosaminoglycans; Horse Diseases; Horses; Interleukin-1; Osteoarthritis; Random Allocation; Recombinant Proteins; Tissue Culture Techniques; Treatment Outcome

Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients. Thus, the aim of the present study was to analyze the effect of CS and HA (500-730 kDa) on MMP-3 synthesis induced by interleukin-1beta (IL-1beta) in chondrocytes from patients with hip OA. Chondrocyte cultures were incubated for 48 h with IL-1beta (2.5 ng/ml) in the absence or presence of different HA 500-730 kDa (Hyalgan, Bioibérica Farma, Barcelona, Spain) concentrations, or alternatively, CS (Condro.san, Bioibérica Farma) at concentrations of 10, 50, 100, 150, 200 and 1,000 microg/ml. The results revealed that both CS and HA (500-730 kDa) inhibited MMP-3 synthesis induced by IL-1beta in human OA chondrocytes. Specifically, CS and HA (500-730 kDa) reduced MMP-3 expression levels at all tested concentrations. Therefore, our study provides new data on the mechanism of action of these drugs, which could help to explain their clinical efficacy in OA patients.

Topics: Adjuvants, Immunologic; Adult; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Female; Humans; Hyaluronic Acid; Interleukin-1; Male; Matrix Metalloproteinase 3; Matrix Metalloproteinase Inhibitors; Osteoarthritis

Topics: Animals; Biological Availability; Chondroitin Sulfates; Drug Therapy, Combination; Glucosamine; Horse Diseases; Horses; Osteoarthritis; Treatment Outcome

The therapeutic effect of glucosamine hydrochloride (GH) and chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1 derivative, on the development of cartilage lesions was investigated in an animal model of osteoarthritis (OA).. The OA model was created by partial medial meniscectomy of the right knee joint (day 0). The rabbits were placed into three experimental groups: operated (OA) rabbits that received placebo treatment, OA rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day 3 and continued for 8 weeks. Macroscopic and histologic analyses were performed on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated by immunohistochemistry.. Only the group receiving combined treatment with GH + CS + fursultiamine showed a significant reduction in the severity of macroscopic and histologic lesions on tibial plateau, which is the weight bearing cartilage surface of the tibia, compared with placebo-treated OA rabbits. This treatment group also revealed a small, but significant, decrease in the body weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in superficial layer stained positive for MMP-1 compared with unoperated control. Rabbits treated with the GH + CS + fursultiamine revealed a significant reduction in the level of MMP-1.. These results suggest that the chondroprotective effect of GH + CS is enhanced by the addition of fursultiamine in experimental OA. This effect was associated with a reduction in the level of MMP-1, which are known to play an important role in the pathophysiology of OA lesions.

Topics: Animals; Body Weight; Cartilage; Chondroitin Sulfates; Disease Models, Animal; Disease Progression; Fursultiamin; Glucosamine; Immunohistochemistry; Male; Matrix Metalloproteinase 1; Osteoarthritis; Protective Agents; Rabbits; Tibia

Macromolecules of the articular cartilage extracellular matrix released into synovial fluid, blood, or urine can serve as potentially useful biomarkers of the severity of osteoarthritis (OA). Biomechanical factors play an important role in OA pathogenesis, yet their influence on biomarker production is not well understood. The goal of this study was to examine the hypothesis that dynamic mechanical stress influences the release of these biomarkers from articular cartilage.. Explants of porcine cartilage were subjected to dynamic compression at 0.5 Hz for 24h at stresses ranging from 0.006 to 0.1 MPa. The concentrations of cartilage oligomeric matrix protein (COMP), keratan sulfate (KS measured as the 5 D 4 epitope), total sulfated glycosaminoglycan (S-GAG), and the KS (keratanase-digestible) and chondroitin sulfate (CS) (chondroitinase-digestible) fractions of S-GAG were measured. Radiolabel incorporation was used to determine the rates of proteoglycan and protein synthesis.. The magnitudes of mechanical stress applied in this study induced nominal tissue strains of 4-23%, consistent with a range of physiological to hyperphysiologic strains measured in situ. COMP release increased in proportion to the magnitude of dynamic mechanical stress, while KS, CS and total S-GAG release increased in a bimodal pattern with increasing stress. Protein and proteoglycan synthesis were significantly decreased at the highest level of stress.. Mechanical stress differentially regulates the turnover of distinct pools of cartilage macromolecules. These findings indicate that mechanical factors, independent of exogenous cytokines or other stimulatory factors, can influence the production and release of OA-related biomarkers from articular cartilage.

Topics: Animals; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Extracellular Matrix Proteins; Female; Glycoproteins; Glycosaminoglycans; In Vitro Techniques; Keratan Sulfate; Matrilin Proteins; Osteoarthritis; Radiopharmaceuticals; Stress, Mechanical; Swine

Fourier Transform Infrared Imaging (FTIRI) is a new method for quantitatively assessing the spatial-chemical composition of complex materials. This technique has been applied to examine the feasibility of measuring changes in the composition and distribution of collagen and proteoglycan macromolecules in human osteoarthritic cartilage. Human cartilage was acquired post-operatively from total joint replacement patients. Samples were taken at the site of a focal lesion, adjacent to the lesion, and from relatively healthy cartilage away from the lesion. Sections were prepared for FTIRI and histochemical grading. FTIRI spectral images were acquired for the superficial, intermediate, and deep layers for each sample. Euclidean distance mapping and quantitative partial least squares analysis (PLS) were performed using reference spectra for type-II collagen and chondroitin 6-sulphate (CS6). FTIRI results were correlated to the histology-based Mankin scoring system. PLS analysis found relatively low relative concentrations of collagen (38 +/- 10%) and proteoglycan (22 +/- 9%) in osteoarthritic cartilage. Focal lesions were generally found to contain less CS6 compared to cartilage tissue adjacent to the lesion. Loss of proteoglycan content was well correlated to histological Mankin scores (r=0.69, p<0.0008). The evaluation of biological tissues with FTIRI can provide unique quantitative information on how disease can affect biochemical distribution and composition. This study has demonstrated that FTIRI is useful in quantitatively assessing pathology-related changes in the composition and distribution of primary macromolecular components of human osteoarthritic cartilage.

Topics: Cartilage, Articular; Chondroitin Sulfates; Collagen; Extracellular Matrix; Histology; Humans; Osteoarthritis; Radiology; Spectroscopy, Fourier Transform Infrared

To determine whether glucosamine and chondroitin sulfate (CS) at concentrations approximating those achieved in plasma by oral administration would influence gene expression of selected mediators of osteoarthritis in cytokine-stimulated equine articular chondrocytes.. Samples of grossly normal articular cartilage obtained from the metacarpophalangeal joint of 13 horses.. Equine chondrocytes in pellet culture were stimulated with a subsaturating dose of recombinant equine interleukin (reIL)-1beta. Effects of prior incubation with glucosamine (2.5 to 10.0 microg/mL) and CS (5.0 to 50.0 microg/mL) on gene expression of matrix metalloproteinase (MMP)-1, -2, -3, -9, and -13; aggrecanase 1 and 2; inducible nitric oxide synthase (iNOS); cyclooxygenase (COX)-2; nuclear factor kappaB; and c-Jun-N-terminal kinase (JNK) were assessed by use of a quantitative real-time polymerase chain reaction assay.. Glucosamine at a concentration of 10 microg/mL significantly reduced reIL-1beta-induced mRNA expression of MMP-13, aggrecanase 1, and JNK. Reductions in cytokine-induced expression were also observed for iNOS and COX-2. Chondroitin sulfate had no effect on gene expression at the concentrations tested.. Concentrations of glucosamine similar to those achieved in plasma after oral administration in horses exerted pretranslational regulation of some mediators of osteoarthritis, an effect that may contribute to the cartilage-sparing properties of this aminomonosaccharide. Analysis of results of this study indicated that the influence of CS on pretranslational regulation of these selected genes is limited or lacking.

Topics: ADAM Proteins; ADAMTS4 Protein; Animals; Cartilage, Articular; Chondrocytes; Chondroitin Sulfates; Cyclooxygenase 2; Gene Expression; Glucosamine; Horse Diseases; Horses; Interleukin-1; MAP Kinase Kinase 4; Matrix Metalloproteinases; NF-kappa B; Nitric Oxide Synthase Type II; Osteoarthritis; Procollagen N-Endopeptidase; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chondroitin Sulfates; Consumer Product Safety; Dietary Supplements; Food, Organic; Glucosamine; Joint Diseases; Osteoarthritis; Treatment Outcome

Topics: Chondroitin Sulfates; Cytokines; Glucosamine; Humans; Joints; Osteoarthritis

After prescribing chrondroitin sulfate for the symptomatic treatment of osteoarthritis, it has been observed that some patients with concomitant psoriasis experience a marked improvement of skin lesions. We describe the clinical and histopathological results of the erythematous and desquamative plaques of three patients with osteoarthritis and psoriasis treated with chondroitin sulfate.. Three adult patients with bilateral knee osteoarthritis and long-standing psoriasis characterized by extensive erythematous, desquamative, and hyperkeratotic plaques, which were resistant to different treatment modalities, received 800 mg/day of chondroitin sulfate during two months. Skin biopsies were obtained before and after treatment.. All three patients presented a marked clinical improvement in both pathologies. In addition to a decrease in the thickness of the epidermis (total epidermal thickness, maximal thickness from the basal layer to the beginning of the corneal layer, and maximal thickness of the corneal layer), a decrease in the number of keratinocytes in the proliferative phase, a decrease in the degree of psoriatic activity, and a substitution of parakeratotic keratinization by orthokeratotic keratinization were observed.. The administration of chrondroitin sulfate resulted in a significant clinical and histological improvement of the psoriatic lesions. The confirmation of these preliminary results in future clinical trials could represent an important advance in the therapeutic armamentarium of patients with psoriasis given the excellent safety profile of this drug.

Topics: Aged; Arthritis, Psoriatic; Chondroitin Sulfates; Female; Humans; Male; Middle Aged; Osteoarthritis

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Dinoprostone; Dose-Response Relationship, Drug; Glucosamine; Horse Diseases; Horses; In Vitro Techniques; Matrix Metalloproteinases; Nitric Oxide; Osteoarthritis; Treatment Outcome

Chondroitin sulfate (CS) is a symptomatic slow-acting drug for osteoarthritis (SYSADOA). It should be noted, however, that there is a CS formulation approved as a drug in Europe, with evidenced efficacy and safety demonstrated by clinical trials in osteoarthritic patients. This formulation should therefore be considered as the reference product. This CS is manufactured by Bioibérica (Spain), commercialized in Europe by IBSA (Switzerland) and Bioibérica, and in the United States by Nutramax. Hence, all other CS formulations must demonstrate their bioequivalence with the reference product. Pharmacokinetic studies have shown that oral exogenous CS is absorbed as several metabolites, and the active moiety has not yet been identified. It is thus difficult to establish bioequivalence from plasma concentration against time curves. However, the FDA permits bioequivalence studies comparing the time course of the pharmacological response with two formulations of the same compound. It has been reported that the time course of CS response can be fitted to a modified Hill equation, as follows: E-E0=[(Emax x Ty )/(T50y+Ty)]. Where E is the effect at time T, E0 is the basal effect, Emax is the maximal effect, T50 is the time required to achieve 50% of the maximal effect and y is the sigmoid slope factor. Hence, it is proposed that a generic CS can be compared to the reference product using the Emax, T50, and y values derived by non-linear regression fitting to the modified Hill equation. The reference/test formulation ratio with the 90% confidence intervals (CI) can thus be estimated. If CI for each parameter ratio lies within 0.8-1.2, both CS formulations can be considered as bioequivalent. In the absence of such bioequivalence studies, physicians and patients are advised to use the reference product to obtain the maximal benefit in terms of efficacy and safety.

Topics: Algorithms; Chemistry, Pharmaceutical; Chondroitin Sulfates; Humans; Osteoarthritis; Pain; Pain Measurement; Pilot Projects; Therapeutic Equivalency

Results from our previous studies suggest that surgical induction of anterior disk displacement (ADD) in the rabbit craniomandibular joint (CMJ) leads to histopathological alterations consistent with osteoarthritis. In addition, molecular changes in collagens and glycosaminoglycans (GAGs) were observed using immunohistochemistry. The purpose of the present study was to further characterize those molecular changes in collagens and GAGs using immuno-electron microscopy.. The right joint of 15 rabbits was exposed surgically and all discal attachments were cut except for the posterior attachment (the bilaminar zone). The disc was then repositioned anteriorly and sutured to the zygomatic arch. The left joint was used as a sham-operated control. Ten additional joints were used as non-operated controls. Mandibular condyles were removed 2 weeks following surgery and processed for light and immuno-electron microscopy using colloidal gold-labeled antibodies against collagen type I, II, VI and IX and against keratan sulfate, chondroitin-4 and -6-sulfate, and link protein.. Light microscopic results showed osteoarthritic changes. Immuno-electron microscopy of osteoarthritic cartilage demonstrated a decline in type II collagen, the abnormal presence of type I collagen and loss of type VI and IX collagens. Quantitative colloidal gold immuno-electron microscopy confirmed the depletion of keratan sulfate, chondroitin-4 and -6-sulfate, and link protein in osteoarthritic cartilage.. Anterior disk displacement leads to molecular alterations in both the collagen and the proteoglycans of rabbit condylar cartilage characteristic of osteoarthritis in other synovial joints. These alterations are consistent with loss of the shock absorber function of the cartilage and injury of the underlying bone.

Topics: Animals; Antibodies; Cartilage; Chondroitin Sulfates; Collagen; Collagen Type I; Collagen Type II; Collagen Type IX; Collagen Type VI; Extracellular Matrix Proteins; Gold Colloid; Immunohistochemistry; Joint Dislocations; Keratan Sulfate; Male; Mandibular Condyle; Microscopy, Immunoelectron; Osteoarthritis; Proteins; Proteoglycans; Rabbits; Temporomandibular Joint Disc; Temporomandibular Joint Disorders

Topics: Adult; Aged; Cartilage, Articular; Chondroitin Sulfates; Cysteine; Dietary Proteins; Humans; Methionine; Middle Aged; Osteoarthritis; Sulfates

We studied changes in the morphology of tibial articular cartilage in early guinea pig osteoarthrosis (OA) at 6 and 12 months of age with quantitative light microscopy, and the distribution of chondroitin-4-sulfate with quantitative ultrastructural immunolabeling, using the 2/B/6 epitope. Labeling was correlated to previous chromatography findings concerning proteoglycan (PG) concentration in animals of the same age. The cell volume fraction had decreased at 12 months in the superficial zone of cartilage with OA (medial condyle) as well as in cartilage without OA (lateral condyle), being lower medially than laterally. The PG concentration differed between the zones and matrix compartments. Medially, a reduction in PG concentration occurred between 6 and 12 months in the interterritorial compartment of the two uppermost zones. Laterally, the concentrations increased. In general, the pericellular PG concentration was higher than the interterritorial in the two uppermost zones. The striking variation in structural and labeling responses in the various zones and compartments indicate a heterogeneous tissue response in guinea pig OA that will probably affect sampling in biochemical analyses of cartilage homogenates and synovial fluid.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Epitopes; Guinea Pigs; Immunohistochemistry; Male; Osteoarthritis

Topics: Administration, Cutaneous; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Placebo Effect; Skin Absorption

To test the hypothesis that chondrocytes are more responsive to the chondroprotective agents, glucosamine (glcN) and chondroitin sulfate (CS), under in vitro conditions simulating in vivo joint stress.. Synthetic and anticatabolic activities of bovine articular cartilage were assayed using 35-sulfate labeling and assaying the specific activity of glycosaminoglycans (GAGs) under the conditions of enzyme-induced matrix depletion, heat stress, mechanical compression and cytokine stress.. The response of cartilage to simulated conditions of in vivo stress varies, depending on the type stress and age of the animal. Cartilage from aged animals was more responsive to stress and to glcN and CS. Pronase-induced matrix depletion and mechanical stress increased proteoglycan synthetic activity. Exposure to glcN and CS significantly enhanced this stress response from 85 to 191% and from 40 to 1000%, respectively. Heat stress and stromelysin digestion decreased synthetic activity, which was reversed or normalized on exposure to glcN and CS. Cartilage from young joints was somewhat refractory to the level of stress imposed and to treatment with glcN and CS.. The metabolic response of cartilage from aged animals to glcN and CS under simulated conditions of in vivo stress is significantly greater than that seen in nonstressed or young tissue. By enhancing the "protective" metabolic response of chondrocytes to stress, glcN and CS may improve its ability for repair and regeneration. These observations suggest that these compounds function as biological response modifiers (BRMs), agents which boost natural protective responses of tissues under adverse environmental conditions.

Topics: Animals; Cartilage, Articular; Cattle; Cells, Cultured; Chondrocytes; Chondroitin ABC Lyase; Chondroitin Sulfates; Dose-Response Relationship, Drug; Extracellular Matrix; Glucosamine; Hot Temperature; Hyaluronoglucosaminidase; Matrix Metalloproteinase 3; Osteoarthritis; Pronase; Proteoglycans; Stress, Mechanical

Chondroitin sulfate (CS) has proven to be a valuable therapeutic tool as a symptomatic slow-acting drug for the treatment of osteoarthritis after oral administration. The aim of this study was to assess the absorption of CS of ichthyic origin after oral administration to 20 healthy male volunteers.. Ichthyic origin CS (from shark cartilage, 4 g) was orally administered to 20 healthy human volunteers, and then extracted and purified from plasma over a 48 h period. The polysaccharide absorbed by oral route was characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured.. After oral administration, ichthyic CS plasma levels increased (more than 120%) with a peak concentration at 8.7h, with the increase reaching significance from 4 to 16 h. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 30.86+/-20.79% at 8h). At the same time, 4-sulfated disaccharide increased to a maximum of 51.91+/-25.91% at 6h, and 6-sulfated and disulfated disaccharides appeared in blood, reaching maximum concentrations of 15.24+/-16.60% at 8h and 2.93+/-4.82% at 12h, respectively. Concomitantly, the mean charge density rose from 0.40+/-0.14 at predose to a maximum of 0.72+/-0.22 and 0.72+/-0.21 measured 8 and 12h after ichthyic CS administration.. Ichthyic CS is absorbed slowly, with a t(max)=8.7+/-4.5h and the C(max)averaged 4.87+/-2.05 microg/ml. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules.

Topics: Absorption; Adult; Biological Availability; Chondroitin Sulfates; Electrophoresis, Agar Gel; Humans; Male; Osteoarthritis

The purpose of this study was to evaluate the effect of the administration of meloxicam; carprofen; and a slow-acting disease modifying osteoarthritis agent, that contains chondroitin sulfate, purified glucosamine, and manganese ascorbate (CS-G-M), on thyroid function in dogs. Forty-six healthy (except for osteoarthritis) euthyroid dogs were blindly assigned to 3 treatment groups: meloxicam, carprofen, and CS-G-M. Each group received the recommended dose of the drug for 60 days. Sixteen other osteoarthritic euthyroid dogs, which received a placebo, were used as a control group to validate the study. For all groups, blood samples were collected on days 0, 30, and 60 to evaluate the serum total and free thyroxine, and endogenous thyrotropin concentrations. There were no significant differences among the treatment groups at each time or within each group over a 60-day period for all parameters. Moreover, none of these values were within the hypothyroid range. Based on the results of this study, the administration of meloxicam, carprofen, and CS-G-M did not affect canine thyroid function evaluation.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Carbazoles; Chondroitin Sulfates; Dog Diseases; Dogs; Female; Glucosamine; Longitudinal Studies; Male; Manganese Compounds; Meloxicam; Osteoarthritis; Random Allocation; Thiazines; Thiazoles; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome

Chondrocytes within articular cartilage experience complete unloading between loading cycles thereby utilizing mechanical signals to regulate their own anabolic and catabolic activities. Structural alterations of proteoglycans (PGs) during aging and the development of osteoarthritis (OA) have been reported; whether these can be attributed to altered load or compression is largely unknown. We report here on experiments in which the effect of intermittent loading on the fine structure of newly synthesized chondroitin sulfate (CS) in bovine articular cartilage explants was examined. Tissues were subjected for 6 days to cyclic compressive pressure using a sinusoidal waveform of 0.1, 0.5 or 1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5, 10 or 20 s, followed by an unloading period lasting 10, 100 or 1000 s. During the final 18 h of the culture, cartilage explants were radiolabeled with 50 microCi/ml D-6-[3H]glucosamine, and newly synthesized as well as endogenous CS chains were isolated after proteinase solubilization of the tissue. CS chains were depolymerized with chondroitinase ABC and ACII, and the 3H-digestion products were quantified after fractionation by high-performance anion-exchange chromatography using a CarboPac PA1 column. Intermittently applied cyclic mechanical loading did not affect the proportion of 4- and 6-sulfated disaccharide repeats, but caused a significant decrease in the abundance of the 4,6-disulfated nonreducing terminal galNAc residues. In addition, loading induced elongation of CS chains. Taken together, these data provide evidence for the first time that long-term in vitro loading results in marked and reproducible changes in the fine structure of newly synthesized CS, and that accumulation of such chains may in turn modify the physicochemical and biological response of articular cartilage. Moreover, data presented here suggest that in vitro dynamic compression of cartilage tissue can induce some of the same alterations in CS sulfation that have previously been shown to occur during the development of degenerative joint diseases such as OA.

Topics: Biomechanical Phenomena; Cartilage, Articular; Chondroitin Sulfates; Disaccharides; Humans; In Vitro Techniques; Osteoarthritis; Oxidation-Reduction; Sulfotransferases; Sulfur; Time Factors; Weight-Bearing

To explore the levels of matrix metalloprotease-3 (MMP-3), tissue inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3 chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory arthropathies.. Blood and synovial fluid were obtained from 103 dogs with rupture of the anterior cruciate ligament (ACLR), osteochondritis dissecans (OCD), fragmented coronoid process (FPC), patella luxation (PL), hip dysplasia (HD) or infectious arthritis. Dogs with non-musculosceletal disorders were used as controls. The biomarkers were measured by immunoassays.. Median levels of synovial MMP-3, TIMP-1 and molar ratios of MMP/TIMP-1 were significantly higher in the arthritis than in the control group. The release of 5D4 keratan sulfate epitope and serum 3B3 neoepitope was reduced in arthritis patients. Increases in synovial TIMP-1 in OA were less pronounced and the molar ratio of MMP-3/TIMP-1 remained far below 1.0, demonstrating a surplus of the protease inhibitor. In osteoarthritic patients median levels of synovial 5D4 keratan sulfate were up-regulated after ACLR and PL and were inversely correlated with increasing duration of lameness. Serum TIMP-1 levels were significantly reduced in the joint disorder group when compared with the control group.. Our observations present the TIMP-1 serum level as a potential marker for the detection of degenerative changes in cartilage and also indicate that in canine OA, the MMP-3 mediated matrix destruction is not of major importance. However MMP-3 seems to be a sensitive marker for the local inflammation in canine arthritis.

Topics: Animals; Anterior Cruciate Ligament Injuries; Arthritis, Infectious; Chondroitin Sulfates; Dogs; Epitopes; Hip Dysplasia, Canine; Keratan Sulfate; Matrix Metalloproteinase 3; Osteoarthritis; Osteochondritis Dissecans; Patella; Rupture; Tissue Inhibitor of Metalloproteinase-1; Ulna Fractures

Topics: Acetaminophen; Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Chondroitin Sulfates; Cyclooxygenase Inhibitors; Glucosamine; Humans; Indomethacin; Meta-Analysis as Topic; Osteoarthritis; Osteoarthritis, Knee; Randomized Controlled Trials as Topic

Topics: Acupuncture; Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis; Pain Management; Plants, Medicinal; S-Adenosylmethionine; United States

Sodiumchondroitinsulfate, Condrosulf, is used in osteoarthritis therapy and belongs to the group of symptomatic slow-acting drugs for osteoarthritis. The aim of this study was to investigate the effects of Condrosulf on total proteoglycan synthesis and cell proliferation in human osteoarthritis and healthy juvenile bovine chondrocytes in vitro.. Chondrocytes were grown as monolayers and stimulated for 7 (human cartilage), or 4, 8 and 12 days (bovine cartilage) with different concentrations of Condrosulf (100 micrograms/ml, 500 micrograms/ml, 1000 micrograms/ml, 2500 micrograms/ml and 5000 micrograms/ml). Proteoglycan synthesis was measured by [35S]Sulfate incorporation. The cell proliferation rate was determined using a [3H]Thymidin assay. The expression of the cartilage markers aggrecan and collagen type II was assessed by Northern blot analysis.. We show that the incubation with Condrosulf did not affect proteoglycan synthesis neither in osteoarthritis, nor in healthy chondrocytes under the present culture conditions. Cell proliferation rate was also not increased by Condrosulf stimulation. The results of the Northern blot assays demonstrated a dose-dependent down regulation of aggrecan expression on mRNA level.. These data indicate a lack of direct anabolic effects of Condrosulf on the biosynthetic activity of cultured articular chondrocytes. The well known ease of clinical symptoms, such as pain or swelling under Condrosulf medication may be interpreted by an interaction with pro-inflammatory cytokines.

Topics: Animals; Cartilage, Articular; Cattle; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Humans; Osteoarthritis; Proteoglycans

To compare synovial fluid biomarkers of cartilage metabolism in joints with naturally acquired or experimentally induced cranial cruciate ligament (CCL) rupture and determine correlations with stage and severity of disease in dogs.. 95 dogs with ruptured CCL, 8 dogs with experimentally ruptured CCL, and 24 healthy dogs.. Synovial fluid was assayed for chondroitin sulfate neo-epitopes 3B3(-) and 7D4 and glycosaminoglycan (GAG) concentration. Results were correlated with demographic data, duration of lameness, radiographic osteoarthritis score, and intra-articular lesions.. The 7D4 concentrations and 7D4:GAG in synovial fluid from joints with naturally acquired CCL rupture and experimental CCL transection were similar and significantly greater than values for healthy control joints. The 3B3(-) concentrations in the CCL-deficient groups were not significantly different, although only values in the naturally acquired CCL rupture group were significantly greater than those in the healthy control group. Within the naturally acquired CCL rupture group there was a significant correlation between 3B3(-) and 7D4 concentrations. However, there were no significant correlations between biomarker concentrations and continuous demographic or disease-related variables or differences in biomarker concentrations with different categories of disease.. Synovial fluid biomarker concentrations were significantly increased in joints with secondary osteoarthritis associated with naturally acquired or experimental CCL rupture; however, lack of apparently simple relationships with demographic variables or stage or severity of disease limits their clinical usefulness.

Topics: Animals; Anterior Cruciate Ligament Injuries; Blotting, Western; Cartilage, Articular; Chondroitin Sulfates; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Epitopes; Glycosaminoglycans; Male; Osteoarthritis; Rupture; Synovial Fluid

Topics: Chondroitin Sulfates; Complementary Therapies; Depression; Drug Interactions; Glucosamine; Humans; Hypericum; Massage; Osteoarthritis; Phytotherapy; Plants, Medicinal

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis

To determine the relationship between synovial fluid, chondroitin sulfate disaccharide and hyaluronic acid to differing degrees of experimental temporomandibular joint (TMJ) osteoarthritis (OA).. Twenty-four merino sheep were divided into three groups and had different TMJ surgical procedures to produce OA. Group I; control (six sheep), Group II; disc perforation (nine sheep) and Group III; disc perforation and articular damage (nine sheep). Synovial fluid was collected initially and at sacrifice at 3 months. Chondroitin 4-sulfate, chondroitin 6-sulfate and hyaluronic acid were measured and correlated to the OA histologic score.. The chondroitin-sulfate levels were significantly increased (Group I to Group II P< 0.001; Group I to Group III P< 0.001), the hyaluronic acid levels decreased (Group I to Group II P< 0.01; Group I to Group III P< 0.01) with the increasing OA score.. Chondroitin-sulfate and hyaluronic acid show a correlation with surgically created TMJ osteoarthritis in sheep model.

Topics: Animals; Chondroitin Sulfates; Disaccharides; Hyaluronic Acid; Osteoarthritis; Sheep; Synovial Fluid; Temporomandibular Joint

Topics: Chondroitin Sulfates; Evidence-Based Medicine; Glucosamine; Humans; Osteoarthritis; Research

Although none of these markers currently have any clinical applications, researchers have made strong advances in understanding molecular markers of OA and remain optimistic that the goal of identifying clinically useful markers of OA is attainable.(3-6,8,9) Much of this positive sentiment arises from the large array of molecules that have been identified.(8) Molecular markers of the greatest potential clinical use will be those that allow early detection of OA, permit disease progression to be monitored, or allow efficacy of various treatment regimens to be assessed. Earlier and more sensitive detection of OA changes may increase effective opportunities for treatment intervention during reversible phases of the OA disease process and allow more objective assessment of treatment efficacy and prognosis.(6)

Topics: Animals; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Dog Diseases; Dogs; Femur; Keratan Sulfate; Matrix Metalloproteinase 3; Osteoarthritis; Synovial Fluid

Topics: Chondroitin Sulfates; Glucosamine; Humans; Osteoarthritis

Damage to the meniscus can lead to posttraumatic osteoarthritis. Early markers of joint injury and tissue disease may be useful in developing and administering clinical treatment. We investigated the effects of total medial meniscectomy on biomarkers measured serially in synovial lavage fluid each month for 3 months. Following meniscectomy in dogs, four biomarkers were evaluated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4), the 3B3(-) neoepitope of chondroitin-6-sulfate, and the 3B3(+) chondroitinase-generated epitope of chondroitin-6-sulfate. Meniscectomy led to statistically significant elevations of all four biomarkers, with levels peaking at 4 weeks. By 12 weeks, the level of the 5D4 epitope returned to the preoperative baseline level whereas that of cartilage oligomeric matrix protein, 3B3(-), and 3B3(+) remained above the baseline. Concentrations of these biomarkers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(-) relative to 3B3(+) remained constant in all knees. In contrast, the level of 5D4 relative to 3B3(+) declined over time in the knee operated on but remained constant in the knee not operated on. These results demonstrate a quantitative change in the molecular components of synovial fluid after meniscectomy, as well as a qualitative change evinced by an alteration in the relative proportions of these epitopes. Extensive analyses showed a strong correlation between serum levels of 3B3(-) from the femoral and cephalic veins; however, serum 3B3(-) was not correlated with synovial fluid 3B3(-). These findings support the hypothesis that the concentrations of select cartilage biomarkers in synovial fluid are altered following meniscectomy and are promising tools for objectively monitoring the induction of osteoarthritis in this model system.

Topics: Animals; Bacterial Proteins; Biomarkers; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Dogs; Epitopes; Keratan Sulfate; Male; Membrane Proteins; Menisci, Tibial; Osteoarthritis; Synovial Fluid; Transferases

Topics: Chondroitin Sulfates; Clinical Trials as Topic; Glucosamine; Humans; Osteoarthritis

Topics: Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; National Institutes of Health (U.S.); Osteoarthritis; United States

Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Dietary Supplements; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Glucosamine; Manganese; Osteoarthritis; Rabbits

Matrix degradation and apoptosis are two crucial features of osteoarthrosis (OA), but the relationship between them needs to be clarified. We developed a novel OA model in partial meniscectomisized rats for the assessment in situ of these processes. The surgical procedure used permitted us to identify and remove 30-50% of the meniscus. Furthermore, the inclusion of high impact exercise enhanced the cartilage damage in a short period of time. OA cartilage displayed a rough and eroded surface, fibrosis and even complete loss; we also found hypertrophy, chondrocyte clusters and a disrupted extracellular matrix. As evidence of matrix degradation we found a diminution of the extracellular components such as chondroitin sulfate-4, 6 (CS-4, 6) and proteoglycans (PGs), and an overall increased activity of the PGs-degrading enzyme, stromelysin-1 (SLN-1). Moreover, the frequency of apoptotic chondrocytes increased according to the severity of the matrix degradation, as detected by TUNEL technique and by morphology. All these changes were enhanced in OA rats with high-impact exercise. Trained rats showed a statistically highly significant difference in histological changes compared to untrained animals. We demonstrate that our model can be evaluated according to Mankin's histologically graded parameters. Also, it is an effective method to assess, in situ, apoptosis in an experimentally induced OA. Our results suggest that apoptosis could be involved in matrix degradation and that TUNEL might be a good method for spotting early apoptotic changes which, combined with careful morphological examinations, provide substantial help in improving apoptosis detection.

Topics: Animals; Apoptosis; Cell Count; Chondrocytes; Chondroitin Sulfates; Disease Models, Animal; Extracellular Matrix; Fluorescent Antibody Technique, Indirect; In Situ Nick-End Labeling; Male; Matrix Metalloproteinase 3; Menisci, Tibial; Microscopy, Confocal; Osteoarthritis; Physical Conditioning, Animal; Proteoglycans; Rats; Rats, Wistar

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Drug Therapy, Combination; Female; Humans; Joints; Male; Microcirculation; Middle Aged; Ointments; Osteoarthritis; Treatment Outcome

Topics: Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; Osteoarthritis; S-Adenosylmethionine

The compound Se-75 bis[beta-(N,N,N-trimethylamino-)ethyl]selenide diiodide (Se-75 BISTAES) has been synthesized and its biodistribution in rabbits studied. A high uptake of radioactivity is found in the knee cartilage. Good scans of the knee are obtained by nuclear scintigraphy at 15 minutes after the injection of Se-75 BISTAES. The results of an equilibrium dialysis study show that Se-75 BISTAES binds to chondroitin sulfate and the binding is directly proportional to the chondroitin concentration. It appears that Se-75 BISTAES or its derivative should have potential as an articular imaging agent.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Knee Joint; Osteoarthritis; Rabbits; Radionuclide Imaging; Selenium Radioisotopes

To determine concentrations of chondroitin sulphate (CS) disaccharides in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables differ between different diseases and subsets of OA.. OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA), with 25, 9, and 11 people in each subset respectively. The SF of 13 normal subjects was also volunteered for analysis along with 15 RA patients. Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Concentrations of unsaturated CS disaccharides Deltadi6S and Deltadi4S were measured by capillary zone electrophoresis.. Concentrations of Deltadi6S were lower in RA (5.90 ng/ml) and OA (13.24 ng/ml) fluids compared with normal (21.0 ng/ml) but no significant differences were seen between disease and normal fluids for Deltadi4S (about 4-6 ng/ml). The ratio of Deltadi6S:Deltadi4S were RA

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chondroitin; Chondroitin Sulfates; Disaccharides; Electrophoresis, Capillary; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Fluid

We report here the isolation and sulphation isomer analyses of trisaccharides GalNAcS(beta1,4)GlcA(beta1,3)GalNAcS (in which S indicates sulphate) derived from the non-reducing termini of aggrecan chondroitin sulphate. Rat chondrosarcoma and human aggrecans were digested for 1 h at 37 degrees C with 30 micro-units of endo-chondroitinase ABC per microgram of chondroitin sulphate, and trisaccharides were isolated from the digests by ToyoPearl HW40S gel-filtration chromatography. Four trisaccharide species were identified; their sulphation isomer compositions, as determined by digestion with chondroitinase ACII and fluorescence-based ion-exchange HPLC, were GalNAc4Sbeta1,4GlcAbeta1,3GalNAc4S, GalNAc4Sbeta1,4GlcAbeta1,3GalNAc6S, GalNAc4,6Sbeta1,4GlcAbeta1, 3GalNAc4S and GalNAc4,6Sbeta1,4GlcAbeta1,3GalNAc6S. The abundances of such sequences in chondroitin sulphate on aggrecan from normal (foetal to 72 years of age) and from osteoarthritic human knee cartilages were also established. The results showed that non-reducing terminal GalNAc4S or GalNAc4,6S can be linked to either a 4-sulphated or a 6-sulphated disaccharide, suggesting that the sulphation of the last disaccharide might not have a direct effect on the specificity of chondroitin sulphate terminal GalNAc sulphotransferases. Furthermore, for each aggrecan preparation examined, the 4S-to-6S ratio of all chain interior disaccharides was equivalent to that in the last repeating disaccharides at the non-reducing terminus, suggesting that neither chondroitin 4-sulphotransferase nor chondroitin 6-sulphotransferase shows preferential activity near the chain terminus.

Topics: Adolescent; Aged; Aggrecans; Aging; Animals; Carbohydrate Sulfotransferases; Cartilage, Articular; Chondroitin Lyases; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Chondrosarcoma; Extracellular Matrix Proteins; Humans; Isomerism; Knee Joint; Lectins, C-Type; Oligosaccharides; Osteoarthritis; Oxidation-Reduction; Proteoglycans; Rats; Sulfotransferases; Sulfur; Trisaccharides

Topics: Chondroitin Sulfates; Complementary Therapies; Glucosamine; Humans; Osteoarthritis; Phytotherapy; Rheumatic Diseases

This study was conducted to measure the intra-articular levels of prostaglandin E2 (PGE2), hyaluronic acid, and chondroitin-4 and -6 sulfate in patients with temporomandibular joint (TMJ) internal derangement involving a closed lock, and to see if these levels correlate with the clinical or arthroscopic findings.. Fifteen female patients (16 joints) with a mean age of 36.7 years were diagnosed as having a closed lock by clinical examination and diagnostic MR imaging. The patient's subjective pain was assessed by a visual analog scale (VAS) and a pain questionnaire (pain score), and the interincisal opening was measured. TMJ aspirates were obtained by washing of the joint with saline containing vitamin B12 as a marker for calibration of data. The samples were assayed for PGE2 with a radioimmunoassay, and the concentrations of unsaturated disaccaride isomers of hyaluronic acid (delta di-HA), chondroitin-4 sulfate (delta di-4S), and chondroitin-6 sulfate (delta di-6S) were measured by high-performance liquid chromatography. Immediately after collection of the synovial aspirates, diagnostic arthroscopy was performed on all but three joints to evaluate the severity of synovitis and cartilage degeneration. The degree of arthroscopic pathology was scored quantitatively. Intra-articular levels of PGE2, delta di-HA(HA), delta di-4S(C4S), and delta di-6S(C6S) were compared with patient's age, mouth opening, VAS rating, pain scores, and arthroscopic scores for synovitis and cartilage degeneration.. The PGE2 level did not correlate with the clinical or arthroscopic parameters. HA had a weak correlation with mouth opening (0.54). C4S and C6S were correlated with arthroscopic scores of TMJ degeneration (0.97, 0.89) and with age (0.75, 0.62). The ratio of C4S and C6S to HA was also correlated with the arthroscopic indices of degeneration (0.93, 0.8) and PGE2 level (0.74, 0.69), but not with age.. The PGE2 level in the TMJ synovial fluid does not specifically reflect the intensity of pain or synovitis, but the detection of high concentrations of C4S and C6S, compared with the amount of HA, is a possible marker of proteoglycan degradation in the TMJ.

Topics: Adolescent; Adult; Arthroscopy; Biomarkers; Cartilage; Chondroitin Sulfates; Dinoprostone; Facial Pain; Female; Humans; Hyaluronic Acid; Joint Dislocations; Middle Aged; Osteoarthritis; Pain Measurement; Range of Motion, Articular; Statistics, Nonparametric; Surveys and Questionnaires; Synovial Fluid; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders

The specific aim of this investigation was to assess differences between primary and secondary osteoarthritis (OA) of the temporomandibular joint (TMJ) using clinical evaluation and synovial fluid analysis for proteoglycans.. Arthroscopic surgery was performed on 101 TMJs from patients with significant pain or dysfunction and who had failed to respond to treatment. Joints were assessed for primary and secondary osteoarthritis. Synovial fluid aspirates were obtained and analyzed to determine the levels of keratan sulfate (KS) epitope and a novel 3B3(-) epitope by enzyme-linked immunosorbent assay (ELISA).. Fifty-four patients and 67 joints had OA diagnosed by both clinical examination and arthroscopy. Primary OA was diagnosed in 14 joints (20%), and the remaining 53 joints were regarded as having secondary OA. No differences were detected in the levels of KS in the synovial fluid from the primary and secondary OA joints. Furthermore, the 3B3(-) epitope was not detectable in the synovial fluid aspirates of any TMJ.. Secondary OA is a common disorder of the TMJ. However, there is no apparent difference in the metabolism of the joints with primary and secondary OA as assessed by proteoglycans in the synovial fluid. The apparent absence of the 3b3(-) epitope, in contrast to its presence in OA of other major synovial joints, suggests that there are some differences between the cartilage metabolism of the TMJ and these other joints during OA.

Topics: Adult; Arthroscopy; Cartilage; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Keratan Sulfate; Male; Osteoarthritis; Proteoglycans; Statistics, Nonparametric; Synovial Fluid; Temporomandibular Joint Disc; Temporomandibular Joint Disorders

This study investigated the correlation between temporomandibular joint (TMJ) disease and the composition of glycosaminoglycans (GAGs) components in the synovial fluid (SF).. Synovial fluid (SF) was obtained from 30 TMJs of 28 female patients diagnosed as having a displaced disc with reduction (WR) (seven joints), a displaced disc without reduction (WOR) (13 joints), osteoarthritis (OA) (five joints), or rheumatoid arthritis (RA) (five joints) by MR imaging and clinical examination. After the SF was directly aspirated, It was digested with chondroitinase ABC and hyaluronidase, and the concentration of unsaturated disaccharide isomers of chondroitin 6-sulfate (delta di-6S), chondroitin 4-sulfate (delta di-4S) and hyaluronic acid (delta di-HA) were measured by high-performance liquid chromatography (HPLC) combined with fluorometry. The ratio of delta di-6S or delta di-4S to delta di-HA, and delta di-6S to delta di-4S, were calculated.. There were no significant differences in concentrations of delta di-6S, delta di-4S, or delta di-HA among the groups. The ratio of delta di-6S to delta di-4S was 2.7 +/- 1.4 in OA, 2.6 +/- 0.9 in joints with WOR, 2.9 +/- 1.2 in joints with WR, and 1.3 +/- 0.4 in RA synovial fluid. Differences in the delta di-6S: delta di-4S ratio between RA and the other conditions were statistically significant (P < .05).. These results suggest that the delta di-6S:delta di-4S ratio in the synovial fluid of the TMJ reflects the proteoglycan metabolism of the joint tissues, particularly of the articular cartilage and synovial tissue. This ratio could be used to diagnose joint diseases and to predict articular cartilage destruction or synovial proliferation caused by these diseases.

Topics: Adult; Arthritis, Rheumatoid; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disaccharides; Female; Fluorometry; Glycosaminoglycans; Humans; Hyaluronic Acid; Joint Dislocations; Middle Aged; Osteoarthritis; Paracentesis; Statistics, Nonparametric; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Disc; Temporomandibular Joint Disorders

Osteoarthritis (OA) influences the levels of free intraarticular glucosaminoglycans (GAG). Little is known about the direction--decrease/increase--of these changes, and information on the correlation between GAG levels and the degree of OA is sparse. Objectives of this study were to investigate the correlation between intraarticular levels of sulphated and unsulphated GAG and the degree of experimental OA, the time course of these changes and whether GAG might be useful as a marker for OA. Twenty-one sheep were randomly assigned to three groups: (1) transsection of the posterolateral bundle of the anterior cruciate ligament, ACL (TD), (2) medial meniscectomy (ME), and (3) meniscectomy and resection of the ACL (MV). During follow-up clinical and radiological examinations were done. After screening for intraarticular effusions, a joint tab was performed and the levels of hyaluronic acid and chondroitin sulphate were measured. The radiological scores differ significantly between group TD and groups ME and MV (P < 0.01). Hyaluronic acid levels in ME and MV are significantly higher than in the controls. Significantly increased levels (P < 0.01) of chondroitin sulphate are found 6 months after ME and 1 year following TD. Clinical consequences: Hyaluronic acid levels--at least in the experimental setting--correspond to a certain degree with osteoarthrotic changes: increasing levels were found along with increasing postoperative interval and increasing grade of OA. Chondroitin sulphate, on the other hand seems, to lend itself as a marker for chondromalacia, in other words for prearthrotic deformities and early stages of OA.

Topics: Animals; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Biomarkers; Chondroitin Sulfates; Female; Glycosaminoglycans; Hyaluronic Acid; Knee Injuries; Knee Joint; Menisci, Tibial; Osteoarthritis; Postoperative Complications; Sensitivity and Specificity; Sheep; Tibial Meniscus Injuries

Chondroitin lyase products of aggrecan and small proteoglycans from normal and osteoarthritic cartilages were analyzed for chain internal Deltadisaccharides and terminal mono- or disaccharides. Chondroitin and dermatan sulfate chains from arthritic cartilages were of essentially normal size and internal sulfation but had significantly altered sulfation of the terminal residues. Whereas in normal cartilage, approximately 60% of terminal GalNAc4S was 4, 6-disulfated, it was reduced to approximately 30% in osteoarthritic cartilage. This is most likely due to a lower terminal GalNAc4, 6S-disulfotransferase activity and reveals that metabolic changes in osteoarthritis can affect this distinct sulfation step during chondroitin and dermatan sulfate synthesis. GlcAbeta1,3GalNAc6S-, the mimotope for antibody 3B3(-), was present on approximately 8 and approximately 10% of chains from normal and osteoarthritic cartilages, respectively. 3B3(-) assayed by immunodot blot was within the normal range for most osteoarthritic samples, with only 5 of 24 displaying elevated reactivity. This resulted not from a higher content of mimotope, but possibly from other structural changes in the proteoglycan that increase mimotope reactivity. In summary, chemical determination of sulfation isomers at the non-reducing termini of chondroitin and dermatan sulfate provides a reliable assay for monitoring proteoglycan metabolism not only during normal growth of cartilage but also during remodeling of cartilage in osteoarthritis.

Topics: Adult; Cartilage, Articular; Chondroitin Sulfates; Chromatography, Ion Exchange; Dermatan Sulfate; Glycosaminoglycans; Humans; Isomerism; Knee Joint; Osteoarthritis; Spectrometry, Fluorescence

To determine effects of aging on sulfation of chondroitin sulfate (CS) in articular cartilage and synovial fluid from normal equine middle carpal joints, and to determine whether CS compositional analysis can be used to assess alterations in proteoglycan turnover in degenerative cartilage obtained from horses with carpal osteochondral fractures.. Carpal articular cartilage and synovial fluid from 44 cadavers with normal joints and from 16 Thoroughbred racehorses during routine carpal arthroscopic surgery.. After papain/chondroitinase digestion of cartilage, CS disaccharides (unsulfated disaccharide delta Di0S, and monosulfated disaccharides delta Di4S and delta Di6S) were quantified by capillary zone electrophoresis. The CS was purified from synovial fluid chondroitinase digested, and analyzed. The CS nonreducing terminal residues, N-acetylgalctosamine (galNAc) or glucuronic acid adjacent to a 4-sulfated or 6-sulfated galNAc, were quantified.. In cartilage, the delta Di6S-to-delta Di4S ratio increased with age; in degenerative cartilage, this ratio was not significantly different from the normal value. Percentage of delta Di0S decreased with age and was significantly higher in degenerative than in normal cartilage. The galNAc4S and galNAc4,6S represented > or = 96% of the terminal residues. There was a significant decrease in 6-sulfation of the terminal residues in degenerative cartilage.. 6-Sulfation of internal and terminal CS residues increased with age. Cartilage degeneration in racehorses was accompanied by deposition of CS chains with altered sulfation patterns, in normal and diseased joints of horses > 2 years old, synovial fluid CS was not indicative of cartilage CS and may represent turnover products of a subpopulation of proteoglycan within the matrix.

Topics: Aging; Animals; Carbohydrate Sequence; Cartilage, Articular; Cattle; Cattle Diseases; Chondroitin Sulfates; Disaccharides; Electrophoresis, Capillary; Fetus; Molecular Sequence Data; Osteoarthritis; Reference Values; Synovial Fluid

Chondroitin sulfate is an important and major component of articular cartilage, where it occurs as part of the large proteoglycan, aggrecan. In the early stages of joint disease, both in animal models and in man, there are changes in chondroitin sulfate that affect the chain length and the pattern of sulfation. These changes can be detected by monoclonal antibodies and appear to reflect part of the cellular response by the chondrocytes to damage to the articular cartilage matrix. The specificity of the changes show that the biosynthesis of chondroitin sulfate is under tight cellular control in chondrocytes and suggests that selected patterns of sulphation within chains are expressed to suit different biological functions.

Topics: Aggrecans; Cartilage, Articular; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Extracellular Matrix Proteins; Humans; Joint Diseases; Lectins, C-Type; Osteoarthritis; Proteoglycans

The pharmacokinetics of chondroitin sulfate (CS, Condrosulf, IBSA, Lugano, Switzerland) were investigated in rats and in healthy volunteers using CS tritiated at the reducing end and CS labeled with 131I or 99mTc respectively. A rapid absorption of orally administered CS is observed in rats and in humans when the drug is dissolved in water. Lower and delayed absorption is observed when CS is administered in gastroresistant capsules. The absolute bio-availability is 15 and 12% for rats and humans respectively. The CS shows a tropism for cartilagineous tissues in rats and for knee tissues in humans as demonstrated by scintigraphic analysis with 99mTc-CS. Monomers, oligo and polysaccharides produced by enzymatic hydrolysis of CS appear in the blood and tissues together with native CS. The effects of partially depolymerized (m.m. 3 to 15 kD) and desulfated fractions on human leukocytes were investigated. CS and its fractions inhibit the directional chemotaxis induced by zymosan-activated serum, are able to decrease the phagocytosis and the release of lysozyme induced by zymosan and to protect the plasma membrane from oxygen reactive species. In rats the oral administration of CS significantly decreases granuloma formation due to sponge implants and cell migration and lysosomal enzyme release in carrageenan pleurisy. Compared with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen), CS appears to be more effective on cellular events of inflammation than on edema formation. It is noteworthy that CS is devoid of dangerous effects on the stomach, platelets and kidneys. In synovial fluid of patients requiring joint aspiration, treated orally for 10 days with CS (800 mg/day) the hyaluronate concentration and the intrinsic viscosity significantly increased, while collagenolytic activity, phospholipase A2 and N-acetylglucosaminidase (NAG) decreased. These results give an insight into the mechanism of the anti-inflammatory and chondroprotective actions demonstrated by this drug in a number of clinical trials in patients with osteoarthritis.

Topics: Administration, Oral; Aged; Animals; Anti-Inflammatory Agents; Chondroitin Sulfates; Feces; Female; Humans; Ibuprofen; Indomethacin; Injections, Intravenous; Leukocytes; Male; Middle Aged; Osteoarthritis; Rats; Synovial Fluid; Time Factors; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

APOPTOSIS IN JOINT CARTILAGE: Apoptosis is the physiologically programmed death of cells to be distinguished from necrosis which caused non-programmed cell death. In joint cartilage, more than 50% of the chondrocytes show signs of apoptosis compared with 10% in normal cartilage. ROLE OF NITRIC OXIDE: In osteoarthritis the production of nitric oxide (NO) appears to be increased, inducing apoptosis of articular chondrocytes stimulated by interleukin 1. NO inhibitors can limit the progression of experimentally induced joint lesions in animal models. IN VITRO RESULTS: The protective effect of the chondroitin sulfates CS4 and CS6 against death of chondrocytes exposed to NO has been demonstrated in vitro. Chondrocytes for New Zealand white rabbits were cultivated in the presence of an NO donor for exposure durations from 12 to 72 hours, with or without adding CS 4&6 to the culture medium. After 3 days of culture, NO induced a significant rise in the number of apoptotic chondrocytes. In 70% of the cases, preventive treatment with 100 micrograms/ml CS 4&6 lowered the number of dead cells. This cytoprotective effect reached a mean 28% and was inversely dependent on the duration of exposure to the NO donor.

Topics: Animals; Apoptosis; Cells, Cultured; Chondrocytes; Chondroitin Sulfates; Humans; Nitric Oxide; Osteoarthritis; Rabbits

PROVEN CLINICAL BENEFIT: It has been demonstrated that CS 4&6 administered at the dose of 1200 mg/d for several months is more effective than placebo and as effective as nonsteroidal anti-inflammatory drugs (NSAID) in providing pain relief and improving joint function without risk in subjects with osteoarthritis of the hip and the knee. The beneficial effect persists several weeks after the end of treatment. These advantages should thus have an overall cost-lowering effect. EVALUATION OF THE ECONOMIC IMPACT: A medico-economical study was conducted to reevaluate the beneficial effect of CS 4&6 on the quantity of NSAID prescriptions in France and to determine whether the drug was used correctly in accordance with indications at an adequate dose and treatment duration.. Two databases, IMS a data bank on medical prescriptions in France, and THALES which gives information on prescriptions by 300 general practitioners, allowed a dynamic analysis of the medical files of 11,000 patients with osteoarthritis. ECONOMICAL BENEFIT: The cost of NSAID prescriptions by general practitioners was reduced by an estimated 67% in patients treated with CS 4&6. In terms of the quantity of NSAID used, the reduction in the CS 4&6 treated group was 63% and 85.3% respectively in patients treated by generalists and by specialists. The quantity of NSAIDs prescribed was reduced by two-thirds when CS 4&6 were represcribed. The cost related to CS 4&6 treatment was compensated for by the reduction in physiotherapy costs and by fewer co-prescriptions for gastroprotective drugs. This study confirmed the randomized clinical studies demonstrating that a regimen of CS 4&6 for several weeks at the dose of 1200 mg/d lowers prescriptions of NSAID which can be completely avoided in nearly half the cases.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; France; Humans; Osteoarthritis

To develop a biodegradable, inflammation-responsive microsphere system for the intraarticular delivery of therapeutic proteins.. Microspheres were synthesized by complex coacervation. Radiolabeled protein release and microsphere degradation were assessed by exposing the microspheres to human synovial fluids (SF) and recombinant gelatinase. Microsphere degradation was confirmed by scanning electron microscopy (SEM). Microsphere biocompatibility was evaluated in vitro by incubating the microspheres with human synoviocytes, and in vivo by injection into mouse joints.. Optimal microsphere formulation was developed. Significant (up to 100%) release of encapsulated protein occurred in SF samples with measurable metalloprotease activity, while release was minimal in SF with negligible activity. Dissolution of microspheres exposed to gelatinase was confirmed by SEM. Microspheres were found to be noncytotoxic in vitro, and noninflammatory in vivo.. Microsphere encapsulation is an inflammation-responsive and biocompatible system of protein delivery that holds promise for use in the delivery of therapeutic proteins to the joint.

Topics: Arthritis, Rheumatoid; Biocompatible Materials; Chondroitin Sulfates; Collagenases; Drug Delivery Systems; Gelatin; Gelatinases; Humans; Hydrogen-Ion Concentration; Injections, Intra-Articular; Kinetics; Metalloendopeptidases; Microspheres; Osteoarthritis; Synovial Fluid

The signs and symptoms of osteoarthritis are common complaints seen in patients suffering with chronic temporomandibular disorders (TMD), specifically, internal derangements with a diagnosis of osteoarthritis. With or without the complaints of pain and swelling, joint noises are bothersome and annoying to both the patient and at times, to those seated close to the patient during mealtime. In fact, many patients are driven to seek care by family members because of his or her TMJ noises. For years in veterinarian medicine, glucosamine and chondroitin sulfates have been used to treat symptoms of osteoarthritis. Recently, the use of these two supplements has been recommended for human beings as well. Reports of decreased joint noises, pain and swelling after the administration of therapeutic doses of these supplements have sparked an interest in their possible use in the treatment of osteoarthritis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Chondrogenesis; Chondroitin Sulfates; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis; Temporomandibular Joint Disorders

To determine if a single time point estimation of chondroitin sulphate (CS) or keratan sulphate (KS) epitopes, hyaluronan (HA), or total glycosaminoglycans (GAG) in knee synovial fluid at time of hospital referral can predict subsequent radiographic progression of knee osteoarthritis.. Two groups of hospital referred patients with knee osteoarthritis were compared: (1) a "progressive" group (n = 45), showing further reduction in radiographic joint space of at least one grade (0-3) in at least one compartment; and (2) a "non-progressive" group (n = 25) in whom radiographs showed no change during the mean follow up period of 2.3 years (median 2, range 1 to 5 years). Knee synovial fluid obtained at the first visit was examined by ELISA for: CS epitopes, using monoclonal antibodies 3B3 and 7D4; KS epitope, using monoclonal antibody 5D4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAG were measured by dye binding with 1:9 dimethylmethylene blue.. In patients with bilateral synovial fluid data right and left knee values were closely correlated for all variables. There were no significant differences between CS and KS epitopes, HA, total sulphated GAG, or ratios of individual CS or KS epitopes to total GAG, between progressive and non-progressive groups.. Single time point estimation of CS, KS, HA, or total GAG in synovial fluid does not distinguish radiographically progressive and non-progressive knee osteoarthritis patients followed for two years.

Topics: Aged; Aged, 80 and over; Biomarkers; Chondroitin Sulfates; Disease Progression; Epitopes; Female; Follow-Up Studies; Glycosaminoglycans; Humans; Hyaluronic Acid; Keratan Sulfate; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Fluid

To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process.. OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue.. Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables.. Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Keratan Sulfate; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Fluid

To study how the concentrations of proteoglycans (PGs) and collagen change in various parts of tibial articular cartilage during aging, and to evaluate the development of spontaneous osteoarthrosis (OA) in guinea pigs.. PGs were extracted from guinea pig cartilage samples using 4M guanidine hydrochloride, and the amount of hydroxyproline was determined in the extraction remainder. The molecular size and aggregation of PGs were analyzed by electrophoresis, and the glycosaminoglycan composition was assessed by high-performance liquid chromatography.. The PG concentration was proportional to the load distribution. However, when OA became histologically manifest, the PG concentration decreased by 50% (from a mean of 44 microg to 22 microg per mg fresh tissue) and the collagen level decreased by 40% (from a mean of 17 microg to 10 microg per mg fresh tissue), while the proportion of water increased by 13% (from a mean of 710 mg to 800 mg per mg fresh tissue).. Unmineralized cartilage can, within physiologic load limits, respond to increased mechanical demands by increasing the PG and collagen concentrations. Beyond a certain limit, however, the cartilage can no longer compensate for further increases in stress, which results in cartilage degeneration and losses of matrix constituents. These losses seemed to appear earlier in the disease process than has been described in previous animal models of secondary OA.

Topics: Aging; Animals; Body Weight; Cartilage, Articular; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disease Models, Animal; Electrophoresis; Glycosaminoglycans; Guinea Pigs; Hyaluronic Acid; Male; Osteoarthritis; Proteoglycans

Topics: Animals; Anti-Bacterial Agents; Cartilage; Chondroitin Sulfates; Cytokines; Genetic Therapy; Glucosamine; Glycosaminoglycans; Humans; Hyaluronoglucosaminidase; Joints; Osteoarthritis; Peptides; Protein Synthesis Inhibitors; Tetracyclines

Topics: Aged; Antibodies, Monoclonal; Cartilage, Articular; Chondroitin Lyases; Chondroitin Sulfates; Epitopes; Female; Humans; Immunologic Techniques; Osteoarthritis; Staining and Labeling

To investigate the effect of diacetyl rhein (DAR) on the synthesis, turnover and composition of cartilage in an experimental model of osteoarthritis in beagle bitches.. Osteoarthritis was induced in mature beagle bitches by the transection of the cranial cruciate ligament. Six animals received DAR 20 mg/kg daily for 11 weeks. A matched group received empty capsules daily for the same period. At 11 weeks, articular cartilage was examined for the ratio of the 6:4-sulfated disaccharides of chondroitin and the tissue concentration of hydroxyproline and glycosaminoglycan. In addition, labeling studies were performed to estimate the effect of DAR on proteoglycan synthesis and turnover.. DAR had no effect on body weight or food consumption but induced a mild diarrhea and slightly increased the incidence of vomiting. DAR tended to reduce proteoglycan synthesis, however, DAR did reduce proteoglycan turnover in the femoral cartilage. DAR produced changes in the composition of the osteoarthritic cartilage that could only partly be accounted for by changes in hydration and/or swelling. In addition, it was noted that induction of osteoarthritis increased the ratio of chondroitin 6-sulfated to chondroitin 4-sulfated disaccharides; DAR reduced the ratio in tibial plateau cartilage from osteoarthritic joints compared with untreated tissue from osteoarthritic joints. DAR showed moderate reduction on the biosynthesis of proteoglycans. DAR also produced a reduction in proteoglycan turnover from all anatomical areas compared with non-treated controls in both the lateral and medial femoral condyles.. DAR was well tolerated by the experimental animals, but did not produce significant changes in the synthesis or turnover of proteoglycans. The slight reduction in proteoglycan synthesis may prove to be biologically significant after chronic dosing. DAR's effects on the hydroxyproline and glycosaminoglycan content suggest, however, that it must influence the swelling of cartilage and loss of glycosaminoglycan. This indicates that small changes can translate, to significant differences in cartilage composition over an 11-week time period.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cartilage, Articular; Cells, Cultured; Chondroitin Sulfates; Disease Models, Animal; Dogs; Epitopes; Glycosaminoglycans; Hydroxyproline; Osteoarthritis; Proteoglycans

The purpose of the present study was to determine the usefulness of the monoclonal antibodies 7-D-4 and 3-B-3 as biomarkers of severity of naturally occurring osteoarthritis in the knee joints of adult cynomolgus macaques. The antibodies were used to immunolocate chondroitin sulfate proteoglycan epitopes in articular cartilage or synovial fluid from knee joints with a range in severity of osteoarthritis. The joints were examined radiographically, grossly, microradiographically, and histologically to characterize the severity of disease, and the results of three different methods of proteoglycan analysis (immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analysis) were compared. Subjectively, the degree of positive immunostaining for 7-D-4 was minimal in normal sites and increased as damage to articular cartilage increased. The scores for 7-D-4 immunostaining in the medial tibial plateau (the site most severely involved in this model) were correlated significantly with severity of damage to articular cartilage (p < 0.05, r2 = 0.50), thus supporting the subjective observations. The ratio of 7-D-4 to sulfated glycosaminoglycans in synovial fluid also was correlated with the score for 7-D-4 immunostaining in the medial tibial plateau (p < 0.05, r2 = 0.54) and with the score for 3-B-3 immunostaining in the medial femoral condyle (p < 0.05, r2 = 0.65). There were no significant correlations among scores for 3-B-3 immunostaining, severity scores, and the ratios of 3-B-3 to sulfated glycosaminoglycans in the synovial fluid. By Western blot analysis, both epitopes were sensitive markers of early cartilage damage in young adult monkeys but were less sensitive in older monkeys. This work provides evidence that measurement of the epitope recognized by 7-D-4 in synovial fluid or, by immunohistochemical or Western blot methods, in articular cartilage has potential use as a marker of severity of naturally occurring osteoarthritis.

Topics: Animals; Antibodies, Monoclonal; Arthrography; Blotting, Western; Cartilage, Articular; Chondroitin Sulfates; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Immunohistochemistry; Knee Joint; Macaca fascicularis; Male; Osteoarthritis; Proteoglycans; Synovial Fluid; Tissue Distribution

Compared to controls, the lateral and medial tibial articular cartilage chondroitin sulfate (CS) content in male STR/Ort mice was elevated between 8 and 19 weeks of age, fell at 24-26 weeks and increased again thereafter. The CS cartilage content of CBA mice remained relatively unchanged. Cartilage CS content was measured in female CBA and STR/Ort mice and in male and female Balb C mice, all at 18 weeks of age. In every case the content was much lower than that found in male STR/Ort mice. CS unsaturated disaccharides were analysed by capillary electrophoresis after digestion of the glycosaminoglycans with chondroitinase ABC. Chondroitin-4-sulfate (C4S) was the predominant isomer at all ages in both strains. The C4S:C6S isomer ratio in CBA mice was much higher in the lateral than the medial cartilage. This difference was much less marked in STR/Ort knee joints: these mice have relatively more C6S than CBA mice. Proteoglycans, extracted from STR/Ort and CBA male mouse cartilage, were characterized by large pore gel electrophoresis and Western blotting. All cartilages contained two slow mobility bands identified as aggrecan by the reactivity with the mab 1C6. Both bands contained C4S and C6S chains. A third band of faster mobility contained only C4S and was 1C6 negative. It was present in both strains. Thus the STR/Ort cartilage contained a normal spectrum of murine articular cartilage proteoglycans.

Topics: Animals; Cartilage, Articular; Chondroitin Sulfates; Female; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred Strains; Osteoarthritis; Proteoglycans; Reference Values

The glycosaminoglycan (GAG) and uronic acid (UA) composition of human hip articular cartilage from patients with femoral neck fractures [assumed osteoporosis (OP); n = 12], from patients with osteoarthritis (OA; n = 12) and from normal controls (n = 9) was determined. Full depth tissue samples from the control and OP groups were analysed from the superior, inferior, anterior and posterior regions, while the OA tissue was from cystic (tissue growing on top of cystic bone lesions) and osteophytic regions, from normal and fibrillated resident cartilage and from regions immediately adjacent to eburnated bone. The total sulphated GAG and UA content was reduced in the inferior region of control cartilage compared to the other regions and the values of all regions of the assumed OP group. Cystic regions and OA cartilage adjacent to the bone also showed lower GAG and UA levels than the other regions. The ratios of chondroitin 6-sulphate (C6S) to chondroitin 4-sulphate (C4S) indicated a similar pattern in the different regions of controls and the patient group with femoral neck fracture (OP group). The cystic and osteophytic cartilage of the OA group exhibited lower C6S/C4S ratios than any other region. The levels of dermatan sulphate (DS) in the cartilage of all regions of the OP and control groups were very similar and low, while the tissues of the OA group contained significantly higher amounts, particularly the cartilage from osteophytes. The previously presumed compositional similarity between normal aged and osteoporotic articular hip cartilage was essentially confirmed in a comparative analysis. Significant changes in GAG and UA composition of OA cartilage from distinct regions was also recorded.

Topics: Aged; Cartilage, Articular; Chondroitin Sulfates; Dermatan Sulfate; Female; Femoral Neck Fractures; Femur Head; Glycosaminoglycans; Humans; Iduronic Acid; Male; Middle Aged; Osteoarthritis; Osteoporosis; Uronic Acids

We present details of a method which allows for the determination of chondroitin sulphate turnover in vivo using the guinea pig. Such methods have been utilised to examine the effects of diacetyl rhein, a compound with purported anti-osteoarthritic activity, and several related anthraquinone analogues on the turnover of chondroitin. Since the guinea pig develops spontaneous osteoarthritis, this may give useful information on the potential for such compounds to inhibit the progression of osteoarthritis. The results show that several of the anthraquinones are capable of reducing the turnover of chondroitin 4- but not 6-sulphate. This may indicate potential mechanisms for the breakdown of guinea pig cartilage aggrecans. We propose that these techniques could be useful for the screening of chemical agents with useful activity against osteoarthritis.

Topics: Aggrecans; Animals; Anthraquinones; Cartilage; Chondroitin Sulfates; Extracellular Matrix Proteins; Guinea Pigs; Lectins, C-Type; Male; Osteoarthritis; Proteoglycans

The joint fluid levels of several molecules that reflect the anabolism and catabolism of cartilage matrix and its inflammation were quantitated in patients with primary osteoarthritis (OA) and traumatic arthritis. The carboxy terminal type II procollagen increased in primary OA and traumatic arthritis joint fluid and was thought to be a good marker of the repair response of chondrocytes. We found that the increase of this molecule in the joint correlated well with body mass index in primary OA and the degree of cartilage erosion caused by joint instability in traumatic arthritis. Chondroitin 6-sulfate, an integral part of human aggrecan, was also high in OA and traumatic arthritis joint fluids, and showed a similar distribution with keratan sulfate in each disease group. Stromelysin-1 and tissue inhibitor of metalloproteinases-1 levels in joint fluid were very high in RA, but levels in patients with OA were low. Carboxy terminal type II procollagen appeared most sensitive in the evaluation of risk factors of OA such as obesity and joint instability, compared to other markers tested.

Topics: Chondroitin Sulfates; Glycoproteins; Humans; Knee Joint; Matrix Metalloproteinase 3; Metalloendopeptidases; Osteoarthritis; Peptide Fragments; Procollagen; Procollagen N-Endopeptidase; Synovial Fluid; Tissue Inhibitor of Metalloproteinases

To test the hypothesis that scintigraphic evidence of bone activity will correlate with biochemical evidence of increased matrix turnover in osteoarthritis (OA).. Keratan sulfate epitope (5D4), chondroitin sulfate epitope (3B3), and osteocalcin (OC) were measured in synovial fluid (SF) from 35 patients with knee OA, within 1 month of bone scan.. SF OC levels correlated with 5D4 levels (r = 0.32, P = 0.047) and with abnormalities on scintigraphic scan. Mean OC levels were 47% higher (P = 0.016) in patients with severely abnormal findings on scans compared with levels in patients with mildly abnormal scan findings. No significant association of 5D4 or 3B3 levels and perfusion- or late (bone)-phase scintigraphic abnormalities was found.. These data support the hypothesis that there is an association between late-phase bone scan abnormalities and SF biochemical markers of bone turnover in OA.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Cartilage, Articular; Chondroitin Sulfates; Female; Humans; Keratan Sulfate; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteocalcin; Radionuclide Imaging; Synovial Fluid

Thirteen adult female rabbits underwent unilateral osteotomy of the proximal tibia. In nine animals, 30 degrees of valgus angulation was created; in four animals, osteotomy without angulation was performed. After a 12-week survival period, the knee joints were processed for histology by staining with hematoxylin and eosin and safranin O. Additionally, the chondroitin sulphate epitopes 3-B-3(-) and 7-D-4 were evaluated immunohistochemically as markers of osteoarthritis. Changes of the articular surface of the tibia were visualized by scanning electron microscopy. Light microscopic evaluation by the Mankin et al. scoring system revealed mild or moderate damage of the cartilage in the lateral compartment of angulated extremities when compared with the control side. Immunohistology with the monoclonal 3-B-3 and 7-D-4 antibodies showed no increased expression of these epitopes in the lateral compartments of the knee. Scanning electron microscopic evaluation of the tibial surfaces revealed slight surface damage localized to the central, weight-bearing portion of the lateral tibial plateau of angulated extremities. Angulation of 30 degrees led to only mild degenerative changes of the cartilage. These results indicate that, in the short term, cartilage has considerable capacity to withstand the effects caused by severe angulation of the limb.

Topics: Animals; Bone Malalignment; Cartilage, Articular; Chondroitin Sulfates; Female; Hindlimb; Immunoenzyme Techniques; Osteoarthritis; Osteotomy; Rabbits; Stress, Mechanical; Synovial Membrane; Tibia; Weight-Bearing

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.

Topics: Adult; Aged; Aged, 80 and over; Aggrecans; Arthritis, Rheumatoid; Cartilage; Chondroitin Sulfates; Epitopes; Extracellular Matrix Proteins; Female; Humans; Keratan Sulfate; Lectins, C-Type; Male; Middle Aged; Osteoarthritis; Proteoglycans; Synovial Fluid

Chondroitin sulphate is the major sulphated glycosaminoglycan present in the extracellular matrix of soft connective tissues and the aim of this study was to investigate the distribution of chondroitin sulphate species in normal and diseased synovium.. Distribution of chondroitin-4-sulphate/dermatan sulphate (Ch4S/DS) and chondroitin-6-sulphate in normal (n = 6), osteoarthritic (n = 4) and rheumatoid (n = 10) synovium was determined using an immunoperoxidase technique and specific monoclonal antibodies to chondroitinase ABC-digested preparations.. Ch4S/DS was expressed throughout the interstitium of all tissues and was also present on blood vessels in rheumatoid samples only. Ch6S was expressed in the lining layer of normal synovium but was absent from this site in osteoarthritic and rheumatoid tissues. Ch6S was also present on all blood vessels in all tissues.. The distinct zonal distributions of Ch4S/DS and Ch6S and their alteration in disease suggest these molecules have different and specific functions in normal and diseased synovium.

Topics: Arthritis, Rheumatoid; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Humans; Immunoenzyme Techniques; Osteoarthritis; Synovial Membrane

Previous studies have shown the presence of a native chondroitin sulfate epitope in articular cartilage proteoglycans from canine knee joints with experimental early osteoarthritis (OA), but not in normal cartilage. The objective of this study was to quantitate the native epitope recognized by monoclonal antibody 3-B-3 in synovial fluids and articular cartilage of diseased joints.. An immunoassay with monoclonal antibody 3-B-3, which recognizes a native chondroitin-6-sulfate structure, was developed and used to analyze synovial fluid lavage material and extracts of articular cartilage from canine knee joints with early experimental OA or with mild disuse atrophy, and from control animals.. The concentration of epitope in the OA fluids was elevated 33-35-fold, and in the OA articular cartilage extracts it was elevated > 200-fold, compared with samples from the control group. No significant difference was detected in the levels of 3-B-3 epitope in the synovial fluid lavage material or cartilage extracts from the joints of the disuse group versus the control group.. The native 3-B-3 epitope in articular cartilage and synovial fluids may be a specific marker of ongoing anabolic events in early degenerative joint disease.

Topics: Animals; Antibodies, Monoclonal; Atrophy; Cartilage, Articular; Chondroitin Sulfates; Dogs; Epitopes; Immunoassay; Osteoarthritis; Synovial Fluid

The present study was undertaken to identify the cartilage matrix molecules that are bound with intermolecular disulfide bonds to IgG and serum albumin molecules recovered from the articular cartilage of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The cartilage specimens were extracted sequentially with three changes of neutral buffer, three changes of 6 M guanidine hydrochloride and then partially degraded with bacterial collagenase. The extracted IgG and albumin, along with matrix molecules bound to these proteins, were isolated with affinity chromatography using antibodies to IgG or human serum albumin conjugated to agarose beads. The isolated materials were characterized with sodium dodecyl sulfate polyacrylamide gel electrophoresis and transfer blotting, using specific antibodies to IgG, albumin, and proteoglycans. In the isolated materials, heteropolymers with IgG or albumin were identified. These polymers contained keratan sulfate and less frequently chondroitin-4-sulfate and chondroitin-6-sulfate. These findings identified the keratan sulfate rich proteoglycans, prevalent at the surface of joint cartilage, as the most common cartilage matrix molecules that are covalently bound to IgG or to serum albumin by disulfide bonds in the articular cartilage of patients with RA or OA.

Topics: Arthritis, Rheumatoid; Cartilage, Articular; Chondroitin Sulfates; Humans; Immunoglobulin G; Keratan Sulfate; Osteoarthritis; Serum Albumin

Canine experimental models of osteoarthritis (OA) and disuse atrophy were used to study cartilage metabolism. The synovial fluids from the OA joints showed elevated levels of keratan sulfate (KS) epitope and link protein, indicating increased catabolism. Analysis of fluids from joints with disuse atrophy showed high levels of KS epitope, but no increase in link protein. Quantitation of a novel chondroitin sulfate (3B3) epitope showed it to be present only in the synovial fluids and articular cartilage of the OA joints. The results indicate that these may be important indicators, or markers, of degenerative joint disease.

Topics: Animals; Atrophy; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Dogs; Keratan Sulfate; Osteoarthritis; Proteoglycans; Synovial Fluid

Changes in the structure of the proteoglycan aggrecan (PG) of articular cartilage were determined immunochemically by RIA and gel chromatography and related to cartilage degeneration documented histologically by the Mankin grading system. Monoclonal antibodies to glycosaminoglycan epitopes were used. In all cartilages, three chondroitin sulfate (CS)-rich populations of large size were observed in addition to a smaller keratan sulfate (KS)-rich population. In grades 7-13 OA cartilages (phase II), molecules were significantly larger than the equivalent molecules of grades 2-6 (phase I). CS chain lengths remained unchanged. In most OA cartilages, a CS epitope 846 was elevated in content, this being most marked in phase II (mean: fivefold). Loss of uronic acid, KS, and hyaluronic acid were only pronounced in phase II OA because of variations in normal contents. Aggregation of PG was unchanged (50-60%) or reduced in OA cartilages, but molecules bearing epitope 846 exhibited almost complete aggregation in normal cartilages. This study provides evidence for the capacity of OA cartilage to synthesize new aggrecan molecules to replace those damaged and lost by disease-related changes. It also defines two phases of PG change in OA: an early predominantly degenerate phase I followed by a net reparative phase II accompanied by net loss of these molecules.

Topics: Aggrecans; Cartilage, Articular; Chondroitin Sulfates; Chromatography; Epitopes; Extracellular Matrix Proteins; Hyaluronic Acid; Lectins, C-Type; Molecular Weight; Osteoarthritis; Proteoglycans

Human chondrocyte strains were derived from explant outgrowth of nonarthritic or osteoarthritic human cartilage. Chondrocytes radiolabeled with [35SO4] or [35S]-methionine were used to measure the biosynthesis of proteoglycans recovered from the most buoyant fraction (A4) of a CsCl density gradient centrifugation performed under associative conditions. The proteoglycans isolated from the A4 fraction (rho < 1.47 g/ml) were hydrodynamically small and contained both large and small glycosaminoglycan chains. When assessed by SDS/PAGE using 3-16% gradient gels, two subpopulations of small proteoglycans (smPG) were identified. The larger of the two species (smPG-I) migrated slower than the 200 kDa marker protein; when reassessed on 3-5% acrylamide gels, its apparent molecular mass was larger than the 480 kDa and 440 kDa alpha and beta heavy chains of dynein. We estimated the apparent molecular size of this smPG to be approximately 520 kDa. The smaller smPG (smPG-II) had an apparent average molecular mass of 180 kDa (range 170-210 kDa) after 3-16% SDS/PAGE. Three monoclonal antibodies, 1C6, 5D4, and S103L, reactive with the hyaluronic acid binding region of the aggregating proteoglycan core protein, keratan sulfate, and a core protein domain in the chondroitin sulfate attachment region, respectively, reacted with a single protein (apparent molecular mass, 180 kDa) that was similar in size to smPG-II.

Topics: Antibodies, Monoclonal; Binding Sites; Cartilage, Articular; Cells, Cultured; Centrifugation, Density Gradient; Chondroitin Sulfates; Chromatography, Gel; Electrophoresis, Polyacrylamide Gel; Humans; Hyaluronic Acid; Keratan Sulfate; Molecular Weight; Osteoarthritis; Proteoglycans

Chondroitin sulfate was administered orally to six healthy volunteers, six patients with rheumatoid arthritis and six patients with osteoarthritis. Blood was collected at intervals before and after treatment and the glycosaminoglycan concentration was analyzed in serum using a sensitive assay based on the metachromatic reaction with 1,9-dimethylmethylene blue. The glycosaminoglycan concentration in serum before and after ingestion of chondroitin sulfate was statistically unchanged in all of the subjects studied. We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory. Any possible benefit to osteoarthritic patients after ingestion of chondroitin sulfate should be sought at the gastrointestinal rather than at the plasmatic or articular cartilage level.

Topics: Administration, Oral; Arthritis, Rheumatoid; Artifacts; Chondroitin Sulfates; Digestive System; Glycosaminoglycans; Humans; Methylene Blue; Osteoarthritis

To investigate the correlation between joint disease and the composition of chondroitin sulfate in the joint fluid, unsaturated disaccharide isomers of chondroitin 4-sulfate (delta di-4S) and chondroitin 6-sulfate (delta di-6S) were measured in joint fluids obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA), or traumatic arthritis (TA).. These pathologic joint fluids were digested with chondroitinase ABC, and the delta di-4S and delta di-6S produced were determined by high performance liquid chromatography combined with fluorometry.. Total content of delta di-4S plus delta di-6S was 71.8 +/- 30.0 nmoles/ml (mean +/- SD) in OA, 55.4 +/- 29.3 nmoles/ml in RA, and 211 +/- 149 nmoles/ml in TA joint fluids. The ratio of delta di-6S to delta di-4S was 3.81 +/- 0.992 in OA, 1.13 +/- 0.527 in RA, and 5.75 +/- 2.46 in TA joint fluids. Differences between groups were statistically significant.. These results strongly suggest that the levels of chondroitin sulfate isomers and the delta di-6S: delta di-4S ratio in joint fluid reflect the proteoglycan metabolism of joint tissues, particularly of articular cartilage; hence, they could be used to diagnose joint diseases and to predict articular cartilage destruction from such joint diseases.

Topics: Aged; Arthritis; Arthritis, Rheumatoid; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Female; Humans; Hyaluronic Acid; Knee Injuries; Knee Joint; Male; Middle Aged; Osteoarthritis; Synovial Fluid

The metabolism of newly-synthesised and total ("resident") proteoglycans was examined in control and osteoarthritic cartilage explants obtained from an experimental model (Pond and Nuki, 1973) of canine osteoarthritis. The following findings were obtained: (i) Non-labelled proteoglycans extracted from normal cartilage with 4 M guanidine HCl showed two bands visualised by staining with toluidine blue. The electrophoretic mobilities of proteoglycans from osteoarthritic cartilage were unchanged but the relative abundance of the slower migrating band increased with time after surgery. (ii) There were qualitative differences in the proteoglycan breakdown products released into the medium of explant cultures of osteoarthritic compared with control cartilage. This was apparent for both labelled and total unlabelled proteoglycans. (iii) There were similarities in the electrophoretic mobilities of the major labelled and non-labelled proteoglycan breakdown products suggesting that total ("resident") proteoglycans and newly-formed proteoglycans were degraded by similar mechanisms. There were however some differences in the labelled and non-labelled proteoglycans, suggesting that the mechanisms of breakdown were not identical. (iv) Immunoblotting techniques showed differences in the distribution of various glycosaminoglycans in proteoglycan breakdown products from control compared with osteoarthritic cartilage explant cultures. (v) Monoclonal antibodies 7-D-4 and 3-B-3 (which recognise unusual native chondroitin sulphate epitopes) showed greatly increased expression on proteoglycans from osteoarthritic cartilage compared with controls.

Topics: Animals; Antibodies, Monoclonal; Binding Sites; Cartilage, Articular; Chondroitin Sulfates; Dogs; Electrophoresis, Polyacrylamide Gel; Female; Glycosaminoglycans; Hyaluronic Acid; Keratan Sulfate; Osteoarthritis; Proteoglycans

Glycosaminoglycans in normal and osteoarthrotic temporomandibular joint disks were studied by means of high-performance liquid chromatography methods. Normal disk tissue contains galactosaminoglycans (chondroitin sulfate and dermatan sulfate) as the main polysaccharides and with smaller amounts of hyaluronate and heparan sulfate. The galactosaminoglycans are mainly sulfated in 6-position, and some of the disaccharides contain iduronic acid. There was a slight general variation in glycosaminoglycan concentration with increasing age. In the severely arthrotic disks the content of glycosaminoglycans was considerably lower than in normal disk tissue. This decrease was far more extensive than that observed in relation to age in normal tissue. The 4/6-sulfate ratio of the galactosaminoglycans was increased, whereas the proportion of iduronic acid was markedly decreased.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cartilage, Articular; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Keratan Sulfate; Male; Middle Aged; Osteoarthritis; Temporomandibular Joint; Temporomandibular Joint Disorders

Horse articular cartilage glycosaminoglycans (GAGs) were measured in synovial fluids from 48 joints affected with osteoarthritis (OA), 22 normal joints, four joints with osteochondritis, three joints with traumatic arthritis and seven joints infected with bacteria. Serum and urine from individual horses were also examined for the presence of GAGs. High levels of GAGs were found in synovial fluids (SF) from horses with OA. In each case, the level was higher in the synovial fluid than in the serum or urine from the same horse. Horses with OA showed high GAG levels in SF, serum and urine compared to horses with normal and infected joints. High levels were also found in horses with osteochondritis and traumatic arthritis. Levels of synovial fluid GAG reflect cartilage destruction in arthritis and may be useful for monitoring disease progression in the equine species.

Topics: Animals; beta-Galactosidase; Chondroitin Lyases; Chondroitin Sulfates; Glycosaminoglycans; Glycoside Hydrolases; Hyaluronic Acid; Hyaluronoglucosaminidase; Keratan Sulfate; Osteoarthritis; Synovial Fluid

Chondroitin sulphate proteoglycans are synthesised by different tissues and cell types, and the chondroitin sulphate chains are variably sulphated. Three monoclonal antibodies 3B3, 7D4 and 6C3 that recognise different native chondroitin sulphate epitopes have been used to investigate changes in structure during embryonic tissue development in the chick and in the response of mature canine articular cartilage during experimental osteoarthritis. Strong focal expression of the epitopes was seen during development of chick bursa, which was different for the three epitopes and which changed during 5 days of development. In embryonic chick limb, although chondroitin sulphate is present throughout the cartilage, the 3B3 epitope, which is at the non-reducing terminus of chains, was only expressed on chondroitin sulphate within one region of the sub-articular cartilage. In mature canine articular cartilage the expression of this epitope on proteoglycans was very low, but when determined 3 or 6 months after induction of experimental osteoarthritis the level was greatly increased in all joints tested (23/23). The abundance of the other two native chondroitin sulphate epitopes was also increased in this experimental disease. The results show that expression of the chondroitin sulphate epitopes detected by the monoclonal antibodies changes during cellular differentiation and development and suggests that it is closely controlled by the cells synthesising chondroitin sulphate chains.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Cartilage, Articular; Chick Embryo; Chondroitin Lyases; Chondroitin Sulfates; Connective Tissue; Dogs; Epitopes; Osteoarthritis

Chondrocyte cultures were developed from the cell outgrowths of explanted human nonarthritic and osteoarthritic human cartilage. Two significant differences in sulfated proteoglycan synthesis were demonstrated between the chondrocytes obtained in this manner. With 35SO4 to measure newly synthesized proteoglycan, we found that chondrocytes derived from osteoarthritic cartilage secreted significantly less (P less than 0.05) high density proteoglycan into the culture medium than did chondrocytes from nonarthritic cartilage after 20 hr of radiolabeling. This reduced amount of high density proteoglycan was sustained when chondrocytes were maintained in unlabeled culture medium ("chase" medium). In addition, the osteoarthritic chondrocytes secreted an increased amount of low density proteoglycan when compared with their nonarthritic counterparts. The elution profile of secreted high density proteoglycan isolated from the osteoarthritic chondrocyte culture medium was assessed by gel filtration on Sepharose CL-2B and revealed the presence of two proteoglycan subpopulations (Kav, 0.25, 0.58), whereas only one proteoglycan series (Kav, 0.37) was seen in the high density fraction of nonarthritic chondrocyte culture medium. Similar gel filtration profiles were also obtained when chondrocytes were maintained in chase medium. The results of this study demonstrated that stable differences in proteoglycan synthesis, but not in intracellular processing, exist between nonarthritic and osteoarthritic chondrocytes. The findings are noteworthy in that these differences were not previously apparent when organ-cultured cartilage was used to assess putative alterations in proteoglycans between the two groups.

Topics: Adolescent; Adult; Aged; Cartilage; Cells, Cultured; Centrifugation, Isopycnic; Child; Child, Preschool; Chondroitin Lyases; Chondroitin Sulfates; Chromatography, Gel; Humans; Kinetics; Middle Aged; Osteoarthritis; Proteoglycans; Sulfates

Temporomandibular joint (TMJ) synovial fluid was aspirated from normal control subjects and patients undergoing surgery for TMJ dysfunction. The glycosaminoglycan (GAG) composition of this fluid was analysed and compared with the clinical diagnosis and histological appearance of the condylar tissues. Changes in GAG composition were observed where a histologically hyperplastic response was seen in joint tissues, but these findings did not necessarily correlate with the initial clinical diagnosis. It is suggested that the fluid composition reflects the current metabolic activities of the tissues and may provide a useful marker of such processes.

Topics: Adult; Chondroitin Sulfates; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Hyperplasia; Male; Mandibular Condyle; Middle Aged; Osteoarthritis; Pilot Projects; Synovial Fluid; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome

Very thin slices of the superficial and deep layers of osteophytic and apparently normal articular cartilage from six human osteoarthritic femoral heads were digested with papain. The digests were analyzed for keratin sulfate content using an enzyme-linked immunosorbent assay (ELISA) with inhibition step, and for chondroitin sulfate and collagen contents using biochemical assays. Although there were marked differences in Safranin-O staining of the superficial and deep layers of osteophytic cartilage, these two layers had identical high ratios of chondroitin sulfate/collagen. Keratan sulfate was present only in small amounts in osteophytic cartilage. However, the deeper layer contained significantly more of this glycosaminoglycan. The deeper layer of articular cartilage contained approximately twice as much chondroitin sulfate and six times more keratan sulfate relative to collagen than the superficial layer. The results of this study showed that this new sensitive approach, which requires as little as 200 micrograms wet cartilage as starting material, provides important qualitative and quantitative information about the major constituents of the matrix.

Topics: Cartilage, Articular; Chondroitin Sulfates; Collagen; Femur Head; Glycosaminoglycans; Humans; Keratan Sulfate; Osteoarthritis; Papain

The intensity of safranin 'O' staining is directly proportional to the proteoglycan content in normal cartilage. Safranin 'O' has thus been used to demonstrate any changes that occur in articular disease. In this study, staining patterns obtained using monoclonal antibodies against the major components of cartilage proteoglycan chondroitin sulphate (anti CS) and keratan sulphate (anti KS), have been compared with those obtained with safranin 'O' staining, in both normal and arthritic tissues. In cartilage where safranin 'O' staining was not detectable, the monoclonal antibodies revealed the presence of both keratan and chondroitin sulphate. Thus, safranin 'O' is not a sensitive indicator of proteoglycan content in diseases where glycosaminoglaycan loss from cartilage has been severe.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Arthritis; Arthritis, Rheumatoid; Cartilage, Articular; Chondroitin Sulfates; Extracellular Matrix; Humans; Immunohistochemistry; Keratan Sulfate; Middle Aged; Osteoarthritis; Phenazines; Proteoglycans

In the cartilage-pannus junction of 14 patients with rheumatoid arthritis (RA) and seven patients with osteoarthritis (OA), monoclonal antibodies to keratan sulphate (KS) and chondroitin sulphate (CS) stained a transitional fibroblastic zone (TFZ) within the pannus in nine RA patients and one OA patient. In three patients this was clearly localised to the cytoplasm of cells in this zone, but in all remaining cases KS and CS could be demonstrated in the surrounding matrix. This area was distinguished from adjacent pannus which contained many blood vessels and cells positive for MHC Class II antigen. Specific markers for glycosaminoglycans have been employed to demonstrate that chondrocyte-derived cells and matrix contribute to the changes seen at the cartilage-pannus junction in RA-affected joints.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; Antibodies, Monoclonal; Arthritis, Rheumatoid; Cartilage, Articular; Chondroitin Sulfates; Female; Histocompatibility Antigens Class II; Humans; Keratan Sulfate; Male; Middle Aged; Osteoarthritis

Salicylates and several other nonsteroidal anti-inflammatory drugs (NSAIDs) that are commonly employed in the treatment of osteoarthritis effectively decrease joint pain and increase mobility. Results from in vitro studies indicate that, in addition, some of these compounds affect proteoglycan metabolism of articular cartilage. Data from in vivo studies suggest that salicylate administration may accelerate articular cartilage damage in several animal models of osteoarthritis. At in vitro concentrations comparable to those that are achieved in the synovial fluid of patients treated with the drug, several NSAIDs suppress proteoglycan synthesis by the chondrocyte. Salicylate has been shown to inhibit the enzymes involved in the early stages of chondroitin sulfate biosynthesis. These NSAID-related effects on chondrocyte metabolism appear unrelated to inhibition of prostaglandin synthetase, and are much more profound in osteoarthritic cartilage than in normal cartilage, due to enhanced uptake of NSAIDs by the osteoarthritic cartilage. Depletion of matrix proteoglycans appears to be a major factor in the increased vulnerability of chondrocytes in degenerating cartilage to effects of NSAIDs. Some NSAIDs may be bound to matrix components. If similar changes occur in the cartilage of patients with arthritis treated with NSAIDs, despite the symptomatic improvement that these drugs produce, cartilage degeneration could be accelerated.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Culture Techniques; Dogs; Humans; Osteoarthritis; Proteoglycans; Salicylates

The chondroitin sulfate-rich region was cleaved from cartilage proteoglycans of experimental osteoarthritic canine joints to establish whether changes in this region of the molecule contribute to the well-documented increase in the chondroitin sulfate to keratan sulfate ratio in osteoarthritis. Experimental osteoarthritis was induced in eight dogs by severance of the right anterior cruciate ligament, the left joint serving as a control. Proteoglycans were extracted from the femoral cartilage of both joints, isolated as A1 fractions by associative density gradient centrifugation and cleaved with hydroxylamine. The chondroitin sulfate-rich region was isolated by either gel chromatography or dissociative density gradient centrifugation. The chondroitin sulfate-rich region from the proteoglycans of the experimental osteoarthritic joints was slightly larger in hydrodynamic size and had both a higher uronate/protein weight ratio and galactosamine/glucosamine molar ratio than the corresponding control. We conclude that the chondroitin sulfate-rich region of proteoglycans in articular cartilage of experimental osteoarthritic joints is larger and has more chondroitin sulfate than that of proteoglycans of normal cartilage.

Topics: Amino Sugars; Animals; Cartilage, Articular; Centrifugation, Isopycnic; Chemical Phenomena; Chemistry; Chondroitin; Chondroitin Sulfates; Dogs; Hydrolysis; Hydroxylamines; Osteoarthritis; Proteoglycans

Topics: Adult; Arthritis, Rheumatoid; Cell Migration Inhibition; Chondroitin; Chondroitin Sulfates; Female; Humans; Leukocytes; Male; Middle Aged; Osteoarthritis

The histopathologic characteristics, in vitro proteoglycan and glycosaminoglycan biosynthesis, and proteoglycan content of osteoarthritic (OA) cartilage tissue types from human femoral heads obtained at the time of total joint replacement were compared. Articular cartilage from fibrillated or discolored cartilage surfaces demonstrated overlapping histopathologic patterns, while cartilage from osteophytic areas was distinct. 35SO4 from each of these three tissue types was found in two peaks of radioactivity on a Sepharose CL-2B column. The average partition coefficient (Kav) of the first peak (peak I) was 0.07, while that of the second (peak II) was 0.63. Proteoglycan monomer predominated in discolored, fibrillated, and osteophytic OA cartilage in peak I. The hydrodynamic size on Sepharose CL-2B of the synthetic proteoglycan monomer was the same for discolored, fibrillated, and osteophytic samples (Kav, 0.25-0.28). Discolored and fibrillated tissues showed a similar percentage of proteoglycan monomer in peak II, whereas osteophyte was reduced in proteoglycan monomer content in peak II. In addition, the endogenous proteoglycans extracted from each cartilage area were generally of a smaller hydrodynamic size than the newly synthesized peak I or proteoglycan monomer. Glycosaminoglycans were predominantly chondroitin 6-sulfate. These results indicated that OA discolored and fibrillated cartilage tissue types from defined topographical areas of human femoral heads possessed neither unique histopathologic nor synthetic or endogenous proteoglycan characteristics. Osteophytic cartilage appeared more histopathologically distinct than either discolored or fibrillated OA cartilage, but synthesized proteoglycan monomer with similar hydrodynamic size to the other cartilage tissue types.

Topics: Aged; Cartilage, Articular; Centrifugation, Isopycnic; Chondroitin Sulfates; Chromatography, Gel; Culture Techniques; Female; Femur Head; Humans; Male; Middle Aged; Osteoarthritis; Proteoglycans; Sulfates

We studied changes in subchondral bone and articular cartilage in an animal model of osteoarthrosis. In this model we applied repetitive impulsive loads to rabbits' knees. Their legs were held in short leg splints so the rabbits were unable to dampen the peak applied load with ankle flexion. After sacrifice, at 1 day to 6 weeks, we studied proximal tibial load-bearing cartilage histologically, biochemically, and with radioactive sulfate uptake. We also studied the subchondral bone under that cartilage histologically, histomorphometrically, with bone scan (99mTc pyrophosphate), and by tetracycline labeling. An increase in 99mTc labeling of the subchondral bone was the first reliable change observed. This was followed by an increase in tetracycline labeling, bone formation, and a decrease in porosity, which has been associated with relative stiffening of bone. Horizontal splitting and deep fibrillation of the overlying articular cartilage followed the early bone changes. All of these changes preceded changes in content and characterization of cartilage proteoglycans or increased chondrocyte activity as manifested by incorporation of radioactive sulfate. In this model the early bone changes preceded changes in the articular cartilage. The deep splitting of articular cartilage occurred prior to metabolic alteration of that tissue.

Topics: Animals; Calcium Pyrophosphate; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Female; Glycosaminoglycans; Keratan Sulfate; Knee Joint; Osteoarthritis; Proteoglycans; Rabbits; Synovial Membrane

The glycosaminoglycans in the menisci of beagles 5--7 years old were analyzed at various times after osteoarthritis was induced by sectioning the anterior cruciate ligament of one knee; the unoperated knee served as control. In the first month after induction, there were signs of inflammation in the operated joint. After 1 week, the water content was elevated and the glycosaminoglycan content (per dry weight) was reduced. The content of keratan sulfate decreased more than that of chondroitin sulfate, but the hyaluronic acid content did not change consistently. The relative proportions of chondroitin-4-sulfate, chondroitin-6-sulfate, and dermatan sulfate remained unchanged. After 3--18 months, the glycosaminoglycan levels reverted to normal, and there was some evidence that after 15--18 months, they were elevated above normal. These results, together with results obtained from single examples of mild and severe osteoarthritis in working foxhounds, suggest that, in contrast to articular cartilage, the meniscus is capable of some regeneration in response to injury.

Topics: Animals; Body Water; Chondroitin Sulfates; Dermatan Sulfate; Dogs; Female; Glycosaminoglycans; Hyaluronic Acid; Keratan Sulfate; Knee; Menisci, Tibial; Osteoarthritis; Uronic Acids

Proteoglycan biosynthesis by human osteochondrophytic spurs (osteophytes) obtained from osteoarthritic femoral heads at the time of surgical joint replacement was studied under defined culture conditions in vitro. Osteophytes were primarily present in two anatomic locations, marginal and epi-articular. Minced tissue slices were incubated in the presence of [(35)S]sulphate or [(14)C]glucosamine. Osteophytes incorporated both labelled precursors into proteoglycan, which was subsequently characterized by CsCl-isopycnic-density-gradient ultracentrifugation and chromatography on Sepharose CL-2B. The material extracted with 0.5m-guanidinium chloride showed 78.1% of [(35)S]sulphate in the A1 fraction after centrifugation. Only 23.0% of the [(35)S]sulphate in this A1 fraction was eluted in the void volume of Sepharose CL-2B under associative conditions. About 60-80% of the [(35)S]sulphate in the tissue 4m-guanidinium chloride extract was associated with monomeric proteoglycan (fraction D1). The average partition coefficient (K(av.)) of the proteoglycan monomer on Sepharose CL-2B was 0.28-0.33. Approx. 12.4% of this monomer formed stable aggregates with high-molecular-weight hyaluronic acid in vitro. Sepharose CL-2B chromatography of fractions with lower buoyant densities (fractions D2-D4) demonstrated elution profiles on Sepharose CL-2B substantially different than that of fraction D1, indicative of the polydisperse nature of the newly synthesized proteoglycan. Analysis of the composition and chain size of the glycosaminoglycans showed the following: (1) preferential elution of both [(35)S]sulphate and [(14)C]glucosamine in the 0.5m-LiCl fraction on DEAE-cellulose; (2) the predominant sulphated glycosaminoglycan was chondroitin 6-sulphate (60-70%), with 9-11% keratan sulphate in the monomer proteoglycan; (3) K(av.) values of 0.38 on Sephadex G-200 and 0.48 on Sepharose CL-6B were obtained with papain-digested and NaBH(4)-treated D1 monomer respectively. A comparison of the synthetic with endogenous glycosaminoglycans indicated similar types. These studies indicated that human osteophytes synthesized in vitro sulphated proteoglycans with some characteristics similar to those of mature human articular cartilage, notably in the size of their proteoglycan monomer and predominance of chondroitin 6-sulphate. They differed from articular cartilage primarily in the lack of substantial quantities of keratan sulphate and aggregation properties associated with monomer inter

Topics: Cartilage; Centrifugation, Density Gradient; Chondroitin Sulfates; Chromatography, Gel; Glucosamine; Glycosaminoglycans; Humans; Hyaluronic Acid; Organ Culture Techniques; Osteoarthritis; Proteoglycans; Sulfates

Topics: Cartilage, Articular; Chondroitin Sulfates; Elasticity; Factor VIII; Glycosaminoglycans; Hip Joint; Humans; Legg-Calve-Perthes Disease; Osteoarthritis

The formation of soluble complexes between alcian blue dye and sulfated glycosaminoglycans provides the basis for the quantitative spectrophotometric estimation of the total concentration of these polysaccharides. Samples containing microgram quantities of sulfated glycosaminoglycan are mixed with a stable dye solution prepared in 15% phosphoric/2% sulfuric acids and absorbance readings at 480 nm are compared to an appropriate standard curve. The method is rapid, convenient, and reproducible. Analyses are performed under conditions in which there is no interference from the non-sulfated glycosaminoglycan hyaluronic acid, or most other anionic macromolecules. In addition, estimations are not effected by small anions or individual monosaccharides. The method has been used for the determination of the purity of commercially available preparations of hyaluronic acid and for the estimation of the sulfated glycosaminoglycan content of various biological fluids including normal human urine and the synovial fluid of individuals with rheumatoid arthritis and osteoarthritis.

Topics: Alcian Blue; Arthritis, Rheumatoid; Chondroitin Sulfates; Glycosaminoglycans; Humans; Osteoarthritis; Spectrophotometry; Synovial Fluid

Topics: Adult; Aged; Bone Matrix; Cartilage, Articular; Chondroitin; Chondroitin Sulfates; Femur Head; Glycosaminoglycans; Humans; Hydrogen-Ion Concentration; Keratan Sulfate; Middle Aged; Osteoarthritis; Staining and Labeling

Biochemical changes and in vitro rates of glycosaminoglycan synthesis were studied in thirty-seven samples of human articular cartilage from nineteen osteoarthritic and four normal control patients who were fifty to seventy-five years old. The samples were compared on the basis of histological grade of the arthritis, and subgroups based on the duration of disease, synovial pathological changes, joint studied, and sex were also compared. The osteoarthritic samples showed a progressive loss of glycosaminoglycans in the cartilage as the histological grade increased. In the early stages of the disease there was an increase in the chondroitin sulphate content as well as in the rate of glycosaminoglycan synthesis in several cases when the values for the osteoarthritic articular-cartilage samples were compared with those for the age-matched controls. In the late stages there was a progressive decrease in the rate of glycosaminoglycan synthesis and a relative decrease in chrondroitin sulphate synthesis compared with keratan sulphate synthesis, and these decreases were highly correlated with the histological grade.

Topics: Aged; Autoradiography; Cartilage, Articular; Cetylpyridinium; Chondroitin; Chondroitin Sulfates; Chromatography, Paper; Dialysis; DNA; Female; Fractional Precipitation; Galactosamine; Glucosamine; Glycosaminoglycans; Hexosamines; Hexuronic Acids; Humans; In Vitro Techniques; Male; Middle Aged; Osteoarthritis; Spectrophotometry; Sulfur Radioisotopes; Uronic Acids

Proteoglycan subunits (PGS) were isolated from bovine articular cartilage of calves and from cows, 18 months and 8 years old respectively. From the latter cartilage of osteoarthrotic and of non-osteoarthrotic sites was taken. PGS were characterized by gel-chromatography on Sepharose 2B columns and subjected to digestion with chondroitinase ABC and with papain. The isolated keratan sulphate-protein cores obtained from chondroitinase digestion were characterized on Sepharose 4B and the chondroitin sulphate chains on Sephadex G-200 gels. A larger molecular size of PGS was found in calf cartilage than in the other samples. This was attributed to the larger molecular size of chondroitin, whereas no change was observed in the keratan sulphate-protein cores. No change was observed in molecular size of PGS, isolated chondroitin sulphates or keratan sulphate-protein cores in osteoarthrosis in comparison with non-osteoarthrotic cartilage from the same joint or from younger adult animals.

Topics: Age Factors; Animals; Cartilage, Articular; Cattle; Centrifugation, Density Gradient; Chondroitin Sulfates; Chromatography, Gel; Keratan Sulfate; Molecular Weight; Osteoarthritis; Proteoglycans

An experimental model of osteoarthritis resulting from laxity of the joint was induced in eighteen mature dogs (at least two years old) by sectioning the anterior cruciate ligament of the right knee (stifle) with a stab incision, the left knee providing a control. A sham operation was also performed in three other dogs, in which a stab incision was made but the ligament left intact. The dogs were killed at various intervals from one to forty-eight weeks later. Morphological changes in bone, cartilage, synovial membrane and joint capsule were examined in all the joints and biochemical changes in the cartilage of three dogs killed after two, eight, and sixteen weeks. All the changes resulting from the operation progressed with time and became indistinguishable from those found in three dogs with natural osteoarthritis of the knee. There were no changes in the joints which had sham operations. As the time of onset is known, this experimental model in a larger species enables a study to be made of the biochemical as well as the morphological changes in the early stages of osteoarthritis.

Topics: Animals; Bone Development; Cartilage, Articular; Chondroitin Sulfates; Disease Models, Animal; Dogs; Female; Femur; Galactosamine; Glucosamine; Keratan Sulfate; Knee Joint; Ligaments, Articular; Male; Menisci, Tibial; Osteoarthritis; Proteoglycans; Stress, Physiological; Synovial Membrane; Tibia; Uronic Acids

Radiochemical and biochemical methods were used to characterize post-mortem and osteoarthrotic femoral head cartilage. Fixed charge density measurements were correlated with glycosaminoglycan content as estimated by uronic acid and hexosamine analyses. In post-mortem cartilage water content decreased from a maximum at the surface to a minimum in the deep zones. In the osteoarthrotic specimens water content was greatest in the middle zones. Glycosaminoglycan content increased with depth and in the osteoarthrotic specimens was reduced throughout the depth of the cartilage. With increasing degeneration there was an increase in water content and decrease in glycosaminoglycan content. The difference in the water content profile in osteoarthrotic cartilage was explained in terms of damage to the collagen network. In osteoarthrosis the latter is no longer capable of restraining the swelling pressure produced by the glycosaminoglycans and swelling is greatest in the midzones, where glycosaminoglycan content is highest.

Topics: Body Water; Cartilage, Articular; Chondroitin Sulfates; Collagen; Femur Head; Glycosaminoglycans; Humans; Keratan Sulfate; Middle Aged; Osteoarthritis

Topics: Chondroitin Sulfates; Galactosamine; Glucosamine; Hip Joint; Humans; Knee Joint; Osteoarthritis; Serologic Tests

Topics: Chondroitin Sulfates; Drug Combinations; Heparin; Hip; Humans; Injections; Injections, Intra-Articular; Joint Diseases; Knee; Osteoarthritis

Topics: Cartilage; Cartilage, Articular; Chondroitin; Chondroitin Sulfates; Osteoarthritis; Polysaccharides; Proteins

Topics: Cartilage; Cartilage, Articular; Chondroitin; Chondroitin Sulfates; Collagen; Humans; Osteoarthritis; Sulfates