chondroitin-sulfates and Cartilage-Diseases

Physical medicine and rehabilitation aim to evaluate, diagnose and treat disability in haemophiliac patients, while preventing injury or deterioration. They also aim to maintain the greatest degree of functional capacity and independence in patients with haemophilia, or to return them to that state. Rehabilitation, together with clotting factor replacement therapy, has revolutionized the management of these patients in developed countries and reduced their morbidity/mortality rates. A knowledge of the musculoskeletal signs and symptoms of haemophilia is essential for providing a treatment which is suitable and customized. Physical medicine and rehabilitation techniques, which are based on physical means, are intended to reduce the impact which these injuries and their consequences or sequelae can have on the quality of life of patients with haemophilia. Under ideal haemostatic control conditions (primary prophylaxis), people with haemophilia could achieve good physical condition which will allow them to enjoy both physical activity and a daily life without limitations. Currently, children undergoing primary prophylaxis are quite close to this ideal situation. For these physical activities to be carried out, the safest possible situations must be sought.

Topics: Bone Cysts; Cartilage Diseases; Cartilage, Articular; Chondroitin Sulfates; Combined Modality Therapy; Electric Stimulation Therapy; Exercise Therapy; Factor IX; Factor VIII; Glucosamine; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Hyaluronic Acid; Hypertrophy; Motor Activity; Musculoskeletal Diseases; Physical and Rehabilitation Medicine; Synovectomy; Synovial Membrane; Synovitis; Transcutaneous Electric Nerve Stimulation

The human cartilage and bone is characterized by a remodeling during the life, well balanced by neosynthesis and degradation of matrix components. In different joint diseases, it becomes imbalanced and the destruction of the cartilage supersedes the repair. In tissue processes in disease and in normal turnover of the matrix, these molecules are fragmented and released into surrounding fluids, in the synovial fluid, and then in the blood and the urine, where they can be detected. The quantitative measurement in the synovial fluid is more specific than in the other body fluids. The research process in recent years has suggested that these molecular markers of cartilage and bone matrix metabolism can be used to determine diagnosis, the disease severity rather than its presence or absence, the prognosis, and the response to therapy. They should help to identify the disease mechanism in different joint diseases not only on the tissue but also on the molecular level. The specific cartilage matrix markers promise to become useful tools in the future in clinical use. The research in this area is still in the early stages, with most results dated from the end of the 1980s and the 1990s.

Topics: Aggrecans; Biomarkers; Cartilage Diseases; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Chondroitin Sulfates; Collagenases; Extracellular Matrix Proteins; Glycoproteins; Humans; Hyaluronic Acid; Joint Diseases; Keratan Sulfate; Lectins, C-Type; Matrilin Proteins; Procollagen; Proteoglycans; Synovial Fluid

Knee bone curvature assessed by MRI was associated with OA cartilage loss. A recent knee OA trial demonstrated the superiority of chondroitin sulfate over celecoxib (comparator) at reducing cartilage volume loss (CVL) in the medial compartment (condyle). The main objectives were to identify which baseline bone curvature regions of interest (BCROI) best associated with CVL and investigate whether baseline BCROI and 2-year change are correlated with the protective effect of chondroitin sulphate on CVL.. This post hoc analysis of a clinical trial used the according-to-protocol population (chondroitin sulphate, n = 57; celecoxib, n = 63) baseline and 2-year MRI to assess bone curvature and CVL. Global optimum search identified the BCROI in the medial condyle using celecoxib as reference. Statistical analyses were performed with Pearson's correlation, Mann-Whitney U -test, Student's t -test and analysis of covariance.. The BCROI including the medial posterior condyle and lateral central condyle was found to correlate best with medial condyle CVL at 2 years ( r = 0.33, P = 0.008). In patients with a baseline BCROI value less than the median (more flattened bone), chondroitin sulphate demonstrated a protective effect on CVL compared with celecoxib in the medial compartment (P = 0.037). In patients with 2-year BCROI changes greater than the median (greater severity of bone flattening), chondroitin sulphate protected against CVL in the medial compartment, condyle and central plateau (P ⩽ 0.030).. This study is the first to demonstrate the feasibility and usefulness of bone curvature measurements to predict effectiveness of OA treatment on CVL. The results identify bone curvature as a potential novel biomarker for knee OA clinical trials.

Topics: Adult; Aged; Bone Diseases; Cartilage Diseases; Cartilage, Articular; Celecoxib; Chondroitin Sulfates; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Female; Humans; Male; Middle Aged; Organ Size; Osteoarthritis, Knee

Magnetic resonance imaging remains the only non-invasive method to assess the quality of cartilage repair procedures, but ideally would be complemented by other modalities, particularly blood tests. Nganvongpanit and colleagues investigated serum levels of hyaluronic acid (HA) and chondroitin sulfate (CS) for their correlation with tissue quality after cartilage repair with autologous chondrocytes versus subchondral drilling in a dog model. They reported better tissue quality in animals treated with chondrocyte implantation. Serum levels correlated with the histological score of biopsy samples: CS showed a negative (r = -0.69) and HA a positive (r = +0.46) correlation. Many questions remain to be answered before serum markers can provide a reliable, non-invasive tool to assess tissue quality, but these data provide an important foundation for additional research.

Topics: Animals; Biomarkers; Cartilage Diseases; Chondrocytes; Chondroitin Sulfates; Dogs; Humans; Hyaluronic Acid

A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functionality and long-term performance of the tissue. Here, we use the biopolymer chondroitin sulphate (CS), one of the major components of cartilage extracellular matrix, to develop a novel bioadhesive that is readily applied and acts quickly. CS was chemically functionalized with methacrylate and aldehyde groups on the polysaccharide backbone to chemically bridge biomaterials and tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with and without cells) bonded to articular cartilage defects. In in vitro and in vivo functional studies this approach led to mechanical stability of the hydrogel and tissue repair in cartilage defects.

Topics: Biocompatible Materials; Cartilage Diseases; Cartilage, Articular; Chondroitin Sulfates; Hydrogels; Tissue Adhesives; Tissue Engineering

To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage.. Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography.. Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084).. The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.

Topics: Adult; Aged; Arthroscopy; Biomarkers; Cartilage Diseases; Cartilage Oligomeric Matrix Protein; Cartilage, Articular; Chondroitin Sulfates; Extracellular Matrix Proteins; Female; Glycoproteins; Humans; Keratan Sulfate; Knee Injuries; Male; Matrilin Proteins; Middle Aged; Osteoarthritis, Knee; Radiography

The effects of cell density on the proliferation and chondroitin sulfate synthesis of chondrocytes embedded in Atelocollagen gel were examined. Chondrocytes of 21 10-week-old Japanese white rabbits isolated by collagenase digestion were embedded in Atelocollagen gel and cultured in Dulbecco's modified Eagles medium at cell densities of 2 x 105 cells/ml (105 group), 2 x 106 cells/ml (106 group), and 2 x 107 cells/ml (107 group) for 4 weeks. Chondrocytes in the 105 group gradually proliferated more than the other two groups. In contrast, most chondrocytes in the 107 group showed increased capability to produce chondroitin 6-sulfate. Cartilage-like tissue was produced from high-density cultures (107 cells/ml), although a decrease in cell number was seen. Even in three-dimensional cultures, the proliferation and chondroitin sulfate synthesis of chondrocytes were influenced by the cell density. These results are informative for the clinical application of chondrocyte transplantation in three-dimensional cultures for cartilage repair.

Topics: Animals; Biomechanical Phenomena; Cartilage Diseases; Cell Count; Cell Culture Techniques; Cell Physiological Phenomena; Chondrocytes; Chondroitin Sulfates; Collagen; Gels; Rabbits; Time Factors; Tissue Engineering

Coronal stepoffs of 0.5 mm (equal to the cartilage height) were created on the medial femoral condyles of adult, skeletally mature rabbits as a model for articular surface incongruity. After 3, 6, 12, and 24 weeks, tissue was analyzed histologically using hematoxylin and eosin and Safranin O staining, autoradiographs were made of the femoral condyles, and immunohistologic analysis was done for 3-B-3(-) and 7-D-4 chondroitin sulfate epitopes. An overlapping flap from the high toward the low side and an increase of the cartilage height on the low side of the defect were observed as permanent features of adaptation throughout the entire followup. Significant degeneration was not seen around the lesion or in the tibial cartilage opposing a stepoff defect. Autoradiography showed a three-phase response to the lesion: an early increase in radiolabeled sulfate (35SO4) uptake, a sharp decline of 35SO4 uptake, and finally a late recovery of the autoradiographic signal indicating partial recovery of proteoglycan synthetic activity. After an early increase, immunohistologic analysis for 3-B-3(-) showed a subsiding tendency by 24 weeks, and the staining with 7-D-4 remained elevated uniformly in the vicinity of the lesion. A rabbit femoral stepoff defect with an offset of 0.5 mm may remodel and not lead to degeneration within the first 6 months after injury in a stable joint.

Topics: Adaptation, Physiological; Animals; Autoradiography; Cartilage Diseases; Cartilage, Articular; Chondroitin Sulfates; Coloring Agents; Disease Models, Animal; Eosine Yellowish-(YS); Epitopes; Female; Femur Head; Fluorescent Dyes; Follow-Up Studies; Hematoxylin; Hindlimb; Immunohistochemistry; Phenazines; Proteoglycans; Rabbits; Radiopharmaceuticals; Range of Motion, Articular; Sulfates; Sulfur Radioisotopes

Cartilage resurfacing by chondrocyte implantation, with fibrin used as a vehicle, was examined in large (12 mm) full-thickness articular cartilage defects in horses. Articular chondrocytes, isolated from a 9-day-old foal, were mixed with fibrinogen and injected with thrombin, in a 1:1 mixture, into 12 mm circular defects on the lateral trochlea of the distal femur of eight normal horses. The contralateral femoropatellar (knee) joint served as a control in which the defect was left empty. Synovial fluid from the femoropatellar joints was sampled on days 0, 4, 7, 30, 120, and 240 postoperatively. Groups of four horses were killed at 4 or 8 months postoperatively, and the repair tissue was evaluated by gross and histologic examination with use of hematoxylin and eosin and safranin O staining and by autoradiography. Biochemical analyses included quantitation of proteoglycan, total collagen, and type-II collagen in the repair tissue. Grossly, grafted defects had improved filling of the cartilage lesions; histologically, these areas consisted of differentiated chondrocytes in the deep and middle zones. The cellular arrangement in these zones resembled that of hyaline cartilage. The control defects contained poorly attached fibrous tissue throughout. Grafted tissue at 8 months had increased proteoglycan synthesis evident by both safranin O staining and autoradiography. Glycosaminoglycan quantitation by dye-binding assay confirmed a significantly elevated glycosaminoglycan content in grafted defects (58.8 micrograms/mg of dry weight) compared with control defects (27.4 micrograms/mg; p < 0.05). Similarly, the levels of chondroitin sulfate/dermatan sulfate was significantly elevated in the grafted defects, and this was the predominant glycosaminoglycan epitope present. There was a statistically significant (p < 0.05) increase in type-II collagen in the grafted tissue at 8 months (61.2% grafted; 25.1% control). This resurfacing attempt with use of allograft chondrocytes, secured in large full-thickness articular defects with polymerized fibrin, resulted in an improved cartilage surface in comparison with the control defects, a significantly greater aggrecan level, and a significantly higher proportion of type-II collagen.

Topics: Animals; Autoradiography; Bone Matrix; Cartilage Diseases; Cartilage, Articular; Cell Separation; Cell Transplantation; Chondroitin Sulfates; Collagen; Female; Fibrin; Horses; Knee Joint; Male; Transplantation, Homologous

We obtained samples of patellar cartilage at the time of surgery from 20 patients: 11 with normal and 9 with macroscopic cartilaginous degeneration. The glycosaminoglycans were separated by cellulose acetate electrophoresis, and the relative content of major glycosaminoglycans was measured by optic scanning. The total content of glycosaminoglycans was estimated by uronic acid analysis. We found that degenerated cartilage contained an increase in dermatan sulfate and hyaluronic acid and a decrease in chondroitin 6-sulfate and total uronic acid concentration, with only slight changes in chondroitin 4-sulfate and keratan sulfate compared with normal cartilage.

Topics: Adolescent; Adult; Cartilage Diseases; Cartilage, Articular; Child; Chondroitin Sulfates; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Keratan Sulfate; Male; Middle Aged; Patella; Uronic Acids

We investigated the diagnostic significance of UDP-D-xylose : proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2.26) in different chronic joint diseases. This enzyme is located almost exclusively within chondrocytes, where it initiates the formation of chondroitin sulphate during the biosynthesis of proteoglycans and from which it is easily released after damage of articular cartilage. Xylosyltransferase activity was determined in synovial fluid and serum by a radiochemical method, based on the incorporation of [14C]xylose from UDP-[14C]xylose into an exogenous acceptor protein. Serum has been shown to be the appropriate material for the determination of xylosyltransferase activity in blood, since in plasma fibrinogen causes an inhibition of enzyme activity of about 50%. The catalytic concentrations of xylosyltransferase in synovial fluids and sera of patients with chronic joint diseases (n = 131) ranged from 0.5 to 22.0 mU/l and from 0.8 to 5.6 mU/l, respectively. On most cases we found higher xylosyltransferase activities in synovial fluids than in the corresponding sera. The highest catalytic concentrations of the enzyme were observed in the synovial fluids of patients suffering from rheumatoid arthritis (median value: 5.56 mU/l, 90%-range: 3.2-22.0 mU/l). Synovial fluids of patients with arthritis urica, however, showing a comparable high degree of inflammation, contained lower enzyme catalytic concentrations (median value: 2.38 mU/l, 90%-range: 0.7-5.2 mU/l), which were in the range of those in osteoarthrosis (median value: 2.50 mU/l, 90%-range: 0.8-4.8 mU/l). The higher xylosyltransferase activities in rheumatoid synovial fluids seem to be attributed to an increased cartilage destruction during the course of this disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Cartilage Diseases; Chondroitin Sulfates; Female; Fibrinogen; Granulocytes; Heparin; Humans; Joint Diseases; Male; Middle Aged; Pancreatic Elastase; Pentosyltransferases; Synovial Fluid; Tissue Extracts; UDP Xylose-Protein Xylosyltransferase

In order to determine if either the proteoglycans or collagen in the cartilagenous epiphyses of a Miniature Poodle with spondyloepiphyseal dysplasia were abnormal, the cartilage was dissociatively extracted in 4 M guanidine HCl in the presence of protease inhibitors and subjected to isopycnic cesium chloride dissociative density gradient ultracentrifugation. Dissociative extraction solubilized 97% of the uronic acid and 88% of the protein. Uronic acid distributed anomalously in the density gradient in that about 1/3 was recovered in each of the D1 (1.58 g/ml), D2 (1.49 g/ml) and D3 (1.44 g/ml) fractions. Proteoglycans in the D1, D2 and D3 fractions also eluted from Sepharose CL-2B columns in a manner indicative of monomers of a smaller apparent hydrodynamic size than those from normal canine growth plate or articular cartilage. D1, D2 and D3 monomers subjected to the sodium borohydride reaction followed by chromatography on a Sepharose CL-6B column yielded glycosaminoglycan chain molecular weights of 10,200 (D1), 7600 (D2) and 6200 (D3). High pressure liquid chromatography on a Whatman Partisil 10PAC column of the chondroitinase AC II digests of D1, D2 and D3 fractions revealed that 60% of the D1, 81% of the D2 and 88% of the D3 unsaturated disaccharides eluted in the delta DiOS-delta DiHA position. Subsequent HPLC of the unsaturated disaccharides on the Hypersil APS column resulted in the recovery of 97% of the nonsulfated unsaturated disaccharides in the delta DiOS position. Associative extraction in 0.5 M guanidine followed by associative gradient ultracentrifugation resulted in the recovery of 27% of the uronic acid in the aA1 and 47% in the aA2 fractions. Two dimensional SDS gel electrophoresis of the CNBr peptides of the collagen isolated by pepsin digestion and 0.9 M NaCl precipitation revealed type II collagen. This study has demonstrated that spondyloepiphyseal dysplasia in a Miniature Poodle is characterized by cartilage containing undersulfated chondroitin sulfate proteoglycan.

Topics: Animals; Cartilage Diseases; Chondroitin; Chondroitin Sulfates; Dog Diseases; Dogs; Growth Plate; Male; Radiography

In order to study human articular cartilage proteoglycans (PG) in aging and pathological states, PG extracts of normal cartilage, osteoarthritic cartilage, chondrosarcoma and osteochondroma were subjected to the density gradient ultracentrifugation in 23% metrizamide-6M urea system. Normal cartilages have chondroitin sulfate rich PG and keratan sulfate rich PG. The latter has a higher buoyant density and increases markedly with aging, but is missing in all of the pathological cartilages tested which have juvenile profiles corresponding to the normal cartilage of a child under 10 years of age. No differences in the chain lengths of glycosaminoglycans were observed in any of the cartilages tested, but marked differences were observed in the aggregation PG and hyaluronate in the pathological cartilages. The molecular sizes of hyaluronate are probably small in normal adults but large in the pathological state. Determinations of hexose and uronate distribution in the density gradient characterize easily the differences in aging and pathological cartilages. This system provided more information than the CsCl-guanidine HCl system.

Topics: Adolescent; Adult; Aged; Aging; Cartilage; Cartilage Diseases; Chondroitin Sulfates; Hexoses; Humans; Keratan Sulfate; Metrizamide; Middle Aged; Proteoglycans; Ultracentrifugation; Uronic Acids

Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embedding technique. Extensive vacuolar changes were observed p--1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.

Topics: Adolescent; Adult; Bone and Bones; Bone Diseases, Developmental; Cartilage; Cartilage Diseases; Child; Chondroitin Sulfates; Collagen; Female; Humans; Hypertrophy; Keratan Sulfate; Proteoglycans; Syndrome

Topics: Adolescent; Bone and Bones; Bone Diseases, Developmental; Calcium; Cartilage; Cartilage Diseases; Child; Chondroitin; Chondroitin Sulfates; Collagen; Female; Glycosaminoglycans; Histocytochemistry; Humans; Keratan Sulfate

Topics: Animals; Cartilage; Cartilage Diseases; Chondroitin; Chondroitin Sulfates; Homozygote; Mice; Mice, Inbred Strains; Species Specificity; Sulfurtransferases