chondroitin-sulfates and Arthritis

Chondroitin sulfate (CS) is a ubiquitous glycosaminoglycan covalently attached to the core proteins of cell surface, extracellular, and intracellular proteoglycans. The multistep and highly regulated biosynthesis of chondroitin sulfate and its degradation products give rise to a diverse species of molecules with functional regulatory properties in biological systems. This review will elucidate and expand on the most recent advances in understanding the role of chondroitin sulfate and its associate proteoglycans, in arthritis and Duchenne muscular dystrophy (DMD), two different and discrete pathologies. Highlighting not only the biodiverse nature of this family of molecules but also the utilization of CS proteoglycans, CS, and its catabolic fragments as biomarkers and potential therapeutic targets for disease pathologies.

Topics: Arthritis; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Humans; Muscular Dystrophy, Duchenne; Proteoglycans

Topics: Administration, Oral; Animals; Arthritis; Chondroitin Sulfates; Cytokines; Humans; Th1 Cells; Th2 Cells

Glucosamine and chondroitin sulphate are naturally occurring substances used by an increasing number of Danish patients with arthritis, although neither of the compounds has been approved for sale in Denmark. Both substances can be taken by mouth and have no known significant side effects. Glucosamine and chondroitin sulphate have been examined in laboratory and animal experiments, and in several clinical studies, which have shown some effect on the symptoms of early or moderate arthritis. The long-term effect has not been evaluated sufficiently and studies of the relation between dose and effect are lacking for both compounds.

Topics: Administration, Oral; Animals; Arthritis; Chondroitin Sulfates; Evidence-Based Medicine; Glucosamine; Humans

Topics: Analgesics; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Chondroitin Sulfates; Delayed-Action Preparations; Drug Combinations; Glucosamine; Humans; Phytosterols; Plant Extracts; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors; Vitamin E

Topics: Arthritis; Chondroitin Sulfates; Complementary Therapies; Evidence-Based Medicine; Exercise; Glucosamine; Humans; Physical Therapy Modalities; Self-Help Devices

This study investigates the hypothesis that arthroscopic biologic glenoid resurfacing without humeral head replacement will provide results similar to humeral hemiarthroplasty in patients aged under 60 years.. Twenty-three consecutive patients aged 15 to 58 years (mean, 32 years) with severe glenohumeral arthritis were prospectively treated with arthroscopic resurfacing of the glenoid with a biologic patch (Restore; DePuy Orthopaedics, Warsaw, IN). Three patients left the study, leaving twenty patients to complete the study. Data collected preoperatively and postoperatively included active and passive range of motion and American Shoulder and Elbow Surgeons (ASES); Constant-Murley; Rowe; University of California, Los Angeles (UCLA); Short Form 12 (SF-12); and visual analog scale (VAS) pain scores. All patients had preoperative and postoperative imaging, either computed tomography scan (n = 2) or magnetic resonance imaging (n = 18), and were re-examined 3 to 6 years after surgery.. At last follow-up, 15 patients (75%) remained satisfied. Five patients had proceeded to have surface replacement arthroplasty, but four of five said that they would undergo the arthroscopic procedure again. Active and passive range of motion improved in flexion (80 degrees to 150 degrees ), abduction (60 degrees to 120 degrees ), external rotation with the arm at the side (10 degrees to 30 degrees ), external rotation in abduction (30 degrees to 70 degrees ), and internal rotation (10 degrees to 50 degrees ). Each rating scale used showed statistically significant (P < .05) improvement from preoperatively to postoperatively: VAS, from 8 to 2; ASES, from 22 (out of 100) to 78; UCLA, from 15 (out of 35) to 29; Rowe, from 55 (out of 100) to 81; and Constant-Murley, from 26 to 79. Six of eight parameters on the SF-12 also showed statistically significant improvements.. Glenoid resurfacing with the Restore patch provided statistically significant improvements for young patients with severe glenohumeral arthritis as measured by the VAS, ASES, UCLA, Rowe, Constant-Murley, and SF-12 scores at 3 to 6 years of follow-up.. Level IV, prospective case series investigating the effect of arthroscopic resurfacing rather than shoulder humeral hemiarthroplasty for grade IV arthritis of the glenohumeral joint.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Animals; Arthritis; Arthroscopy; Bioprosthesis; Chondroitin Sulfates; Combined Modality Therapy; Female; Follow-Up Studies; Glucosamine; Humans; Injections, Intra-Articular; Lubricants; Male; Middle Aged; Physical Therapy Modalities; Prospective Studies; Radiography; Range of Motion, Articular; Recovery of Function; Scapula; Shoulder Joint; Treatment Outcome; Young Adult

We planned to report on the effect of two nonanimal chondroitin sulfates (CSs) with different molecular masses produced using an innovative biotechnological process in an adjuvant arthritis animal model.. The experiments included healthy animals, untreated arthritic animals and arthritic animals having been administered 900 mg/kg of either of the two CS samples daily. Arthritic score, γ-glutamyltransferase (GGT) activity in hind paw joint tissue homogenates, plasmatic C-reactive protein (CRP) and pro-inflammatory cytokines IL-1β and IL-6 were assayed.. Low-molecular-mass (LMM) CS significantly reduced the arthritic score by up to about 30% from 14 to 28 days. In contrast, no significant differences were observed for high-molecular-mass (HMM) CS, even if a trend in its capacity to decrease the arthritic score by up to about 11% was observed. Additionally, LMM CS was able to significantly decrease GGT activity by approximately 31% and plasmatic CRP levels by about 9%. Both nonanimal CS samples were effective in reducing plasmatic levels of proinflammatory cytokines. A greater efficacy was also observed for LMM CS compared with a pharmaceutical-grade CS of extractive origin, while the efficacy of the HMM CS sample was found to be rather similar. The greater effect of LMM CS in reducing arthritic parameters may be related to its lower molecular mass with respect to HMM CS and natural CS.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; C-Reactive Protein; Chondroitin Sulfates; Disease Models, Animal; gamma-Glutamyltransferase; Interleukin-1beta; Interleukin-6; Male; Rats, Inbred Lew; Tarsal Joints

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

Topics: Arthralgia; Arthritis; Chondroitin Sulfates; Delayed-Action Preparations; Humans; Meta-Analysis as Topic; Review Literature as Topic

Macromolecular prodrugs of three non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen, ketoprofen, and naproxen, were prepared by the covalent attachment of the drugs onto chondroitin sulfate (ChS) using PEG 1000 as a spacer. Drug-PEG adducts were synthesized using 1,1'-carbonyl diimidazole as a coupling agent in dimethyl sulfoxide, followed by the reaction with ChS in highly dilute aqueous solution at pH 6.8 via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) as a conjugation agent. The drug-ChS conjugates were confirmed by FTIR, 1H NMR and 13C NMR and the molar percent of drug substitution onto ChS was characterized by 1H NMR using the peak areas of the three protons of -PhiCHCH3 on the drugs to those of -NHCOCH3 on ChS. All drug-ChS conjugates are water-soluble. The release amounts of the free drugs from their corresponding drug-ChS conjugates were evaluated in the presence or absence of either esterase or chondroitinase, and the both enzymes in pH 7.4 Tris-buffer solutions at 37 degrees C by high performance liquid chromatography (HPLC). Keto-ChS conjugates released approximately 100% ketoprofen within 12h in the presence of esterase, but the combination with chondroitinase did not accelerate the release rate. The degradation of Keto-ChS conjugates by chondroitinase was confirmed by gel permeation chromatography (GPC). The Keto-ChS conjugates still retained the enzymatic recognition even at the substitution of ketoprofen as high as 56 mol%. The inhibition percent of carrageenan-induced edema of Keto-ChS-56 was comparable to that of a simple blend of ChS and ketoprofen, suggesting that biologically active ChS and ketoprofen could be liberated from the conjugate.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Carrageenan; Chemical Phenomena; Chemistry, Physical; Chondroitin ABC Lyase; Chondroitin Sulfates; Edema; Excipients; Hydrolysis; Ibuprofen; Ketoprofen; Magnetic Resonance Spectroscopy; Male; Naproxen; Polyethylene Glycols; Prodrugs; Rats; Rats, Wistar; Solubility; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared

In order to evaluate the improvement in the treatment of chronic arthritis, we investigated chondroitin sulfate depolymerization product (low molecular weight chondroitin sulfate, LMWCS) and intact chondroitin sulfate (CS) in vitro and in vivo. LMWCS was prepared by a chemical depolymerization process induced by hydrogen peroxide in the presence of copper salts. LMWCS (300 mg/kg) and CS (1200 mg/kg) were orally administered to DBA/1J mice once daily for 14 d prior to initial immunization with type II collagen. Their elastase activities and the production of cytokines in sera were examined on type II collagen-induced arthritis in DBA/1J mice. We also compared the paracellular transport of LMWCS and CS across Caco-2 cell monolayers and examined the inhibitory effects on elastase activities. LMWCS inhibited elastase activity slightly, but CS did not show inhibition. Hind paw edema was significantly decreased by LMWCS treatment. Levels of anti-type II collagen antibody and tumor necrosis factor-alpha (TNF-alpha) in sera were also reduced by LMWCS treatment but not in case of CS, although no significant difference was observed between LMWCS and CS on interleukin-6 (IL-6) induction. The LMWCS preparation showed preventive effects on the type II collagen-induced arthritis in DBA/1J mice and better permeability through Caco-2 cells.

Topics: Animals; Antibodies; Arthritis; Caco-2 Cells; Cell Membrane Permeability; Chondroitin Sulfates; Collagen Type II; Disaccharides; Edema; Humans; Leukocyte Elastase; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred DBA; Molecular Weight

Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH*), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH* radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH* levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH* production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.

Topics: Animals; Antioxidants; Arthritis; Arthritis, Experimental; Body Weight; Cartilage; Cartilage, Articular; Catalase; Cattle; Chemokine CXCL2; Chemokines, CXC; Chondroitin Sulfates; Collagen; Free Radicals; Glycosaminoglycans; Humans; Hyaluronic Acid; Intercellular Signaling Peptides and Proteins; Joints; Lipid Peroxidation; Male; Monokines; Neutrophils; Pancreatic Elastase; Rats; Rats, Inbred Lew; Vitamin E

Topics: Animal Feed; Animals; Arthritis; Chondroitin Sulfates; Dietary Supplements; Dog Diseases; Dogs

TSG-6 is a secreted 35-kDa glycoprotein, inducible by TNF and IL-1. The N-terminal portion of TSG-6 shows sequence homology to members of the cartilage link protein family of hyaluronan binding proteins. The C-terminal half of TSG-6 contains a so-called CUB domain, characteristic for developmentally regulated proteins. High levels of TSG-6 protein are found in the synovial fluid of patients with rheumatoid arthritis and some other arthritic diseases. Here we show that TSG-6 readily formed a complex with a protein present in human, bovine, rabbit, and mouse serum. This complex was stable during SDS-PAGE under reducing conditions, and in the presence of 8 M urea. The protein that binds TSG-6 was purified from human serum and identified as inter-alpha-inhibitor (I alpha I) by N-terminal microsequencing. Microsequencing of the complex itself revealed the presence of TSG-6 and two of the three polypeptide chains of I alpha I (bikunin and HC2). Experiments with recombinant TSG-6 and I alpha I purified from human serum showed that the TSG-6/I alpha I complex is rapidly formed even in the apparent absence of other proteins at 37 degrees C, but not at 4 degrees C. The TSG-6/I alpha I complex was cleaved by chondroitin sulfate ABC lyase, suggesting that cross-linking by chondroitin sulfate is required for the stability of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alpha-Globulins; Amino Acid Sequence; Animals; Arthritis; Blotting, Western; Cattle; Cell Adhesion Molecules; Cells, Cultured; Chondroitin Sulfates; Chromatography, Affinity; Cross-Linking Reagents; Glycoproteins; Glycosaminoglycans; Humans; Hyaluronic Acid; Mice; Molecular Sequence Data; Precipitin Tests; Rabbits; Recombinant Proteins; Trypsin Inhibitors; Tumor Cells, Cultured

The concentrations of hyaluronan (HA) and chondroitin sulfate (CS) in synovial fluids from patients with traumatic arthritis (TA) with and without hydrarthrosis were measured. The CS in synovial fluids was determined as a marker of cartilage destruction by high performance liquid chromotography. The concentration of HA in synovial fluids was lower in patients with hydrarthrosis than in healthy volunteers and patients with TA without hydrarthrosis, whereas the total amounts of HA and CS and the concentration of CS were higher in patients with hydrarthrosis. To investigate the relation between hydrarthrosis and production of HA in synovial tissues, TA synovial tissue biopsies were stained for HA with biotinylated HA binding region. The intensity of HA staining was higher in specimens from patients with hydrarthrosis than in normal and TA without hydrarthrosis specimens. Thus, there may be a correlation between hyperproduction of HA, cartilage destruction and increase in fluid volume in TA.

Topics: Adolescent; Adult; Anterior Cruciate Ligament Injuries; Arthritis; Chondroitin Sulfates; Female; Humans; Hyaluronic Acid; Hydrarthrosis; Male; Microscopy, Electron; Synovial Fluid

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

Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.

Topics: Animals; Arthritis; Cartilage, Articular; Chondroitin Sulfates; Dermatan Sulfate; Disease Models, Animal; Evaluation Studies as Topic; Hyaluronic Acid; Immobilization; Injections, Intra-Articular; Keratan Sulfate; Knee Joint; Rabbits; Uronic Acids

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

The timing and molecular profile of cartilage destruction in Escherichia coli and Staphylococcus aureus infectious arthritis and killed Mycobacterium butyricum adjuvant arthritis are presented. Infectious arthritis was studied for 3 weeks; cartilage samples were analyzed at 2, 10, and 21 days. At 48 h postinfection, glycosaminoglycan content was reduced by 20% (p less than 0.05) in E. coli infected knees and by 42% (p less than 0.05) in tibial plateau cartilage of S. aureus infected knees. By the 3rd week of infection, glycosaminoglycan losses amounted to as much as 73% (p less than 0.005). In comparison, collagen losses were not significant prior to the 3rd week of infection, at which time 42% (p less than 0.05) was lost. Adjuvant arthritic tibial plateau cartilage was examined at 1, 3 and 12 weeks. Glycosaminoglycans decreased by 42% the 1st week, plateauing at 62% by the 3rd and 12th weeks. Collagen degradation began at 3 weeks (28% loss, p less than 0.10) and by the 12th week was reduced by 49% (p less than 0.005). Analysis of the individual species of glycosaminoglycan showed a parallel loss of chondroitin sulfate and keratan sulfate. Fractionation of glycosaminoglycans with respect to size produced no evidence of shortened chains in cartilage from infected joints. Hyaluronic acid losses were greatest when collagen was significantly decreased. The pattern by which chondroitin and keratan sulfates are lost demonstrates that a prominent feature of infectious and noninfectious inflammatory arthritis is a rapid loss of proteoglycan subunits that precedes collagen loss.

Topics: Animals; Arthritis; Arthritis, Experimental; Arthritis, Infectious; Cartilage, Articular; Chondroitin Sulfates; Chromatography, Gel; Collagen; Escherichia coli Infections; Hyaluronic Acid; Keratan Sulfate; Mycobacterium; Rabbits; Staphylococcal Infections; Time Factors

Proteoglycan alterations were studied in articular cartilage obtained from control and antigen induced arthritis of the rabbits. Agarose/polyacrylamide-gel electrophoretic patterns of proteoglycan revealed heterogeneity in each experiment. In the cartilage of the antigen induced arthritis the following changes were demonstrated at the early stage; 1) an increase in the non-aggregated proteoglycan content, 2) a decrease in the size of the proteoglycan, 3) a decrease in the ability to interact with hyaluronic acid, 4) a constancy in the length of the glycosaminoglycan chains, 5) a decrease in hexuronate/protein, galactosamine/glucosamine and galactosamine/amino acid ratio, and 6) a decrease in serine and threonine content of the core protein. At the late stage the following changes were most pronounced; 1) a recovery in the size of the proteoglycan, 2) a marked decrease in the ability to interact with hyaluronic acid, 3) an increase in galactosamine/glucosamine and a gradual decrease in glucosamine/amino acid ratio, and 4) an increase in serine and glycine and a decrease in half cysteine and methionine content of the core protein. The results indicate that the smaller size of the proteoglycan from articular cartilage was due to degradation of the core protein at the early stage. But there seems to be some changes of proteoglycan synthesis at the late stage.

Topics: Amino Acids; Animals; Arthritis; Arthritis, Experimental; Cartilage, Articular; Chondroitin Sulfates; Electrophoresis, Polyacrylamide Gel; Glycosaminoglycans; Proteoglycans; Rabbits

Glycosaminoglycan content and cell density of articular cartilage have been studied quantitatively in the adult rabbit in experimental lipoarthrosis. On the fourth day after injection of non-radioactive or tritium-labelled glyceryl trioleate into the synovial cavity of the knee joint, femoral condylar cartilage shows no change in cellularity. There is a 35% loss of chondroitin sulphate from the matrix, but little change in keratansulphate. The results are not affected by the presence or absence of radioactive isotope in the lipid: possible mechanisms accounting for glycosaminoglycan loss are discussed.

Topics: Animals; Arthritis; Cartilage, Articular; Cell Count; Chondroitin Sulfates; Glycosaminoglycans; Joint Diseases; Keratan Sulfate; Rabbits

Prolonged treatment of rabbits with an established bilaterally symmetrical experimental arthritis with prednisolone (0.5 mg/kg day) reduced both the swelling and the histopathological changes in the arthritic joints whereas short-term treatment suppressed only the swelling. Such prolonged treatment also suppressed both the humoral and cell-mediated immune responses measured systemically in these animals and the cell-mediated immune responsiveness of the synovium determined by lymphokine production by cultured explants. The results suggested that the suppressive effect of the drug on the arthritis was related to the inhibition of cell-mediated immune responsiveness. Prednisolone treatment also had deleterious effect on cartilage proteoglycan metabolism determined both histologically and biochemically. Intra-articular administration of triamcinolone hexacetonide (three injections of 2 mg per joint at fortnightly intervals) also reduced the swelling and histopathological changes, although there was no effect on circulating antibody levels.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Antibodies; Arthritis; Arthritis, Experimental; Cartilage, Articular; Chondroitin Sulfates; Immunity, Cellular; Prednisolone; Rabbits; Triamcinolone Acetonide

Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.

Topics: Animals; Arthritis; Cartilage, Articular; Chondroitin; Chondroitin Sulfates; Culture Techniques; Dextrans; Knee Joint; Proteoglycans; Rabbits; Sulfates; Synovial Membrane

Proteoglycans extracted from normal and arthritic bovine articular cartilage of various ages were fractionated and purified under associative and dissociative conditions. After proteolytic digestion, the composition of the acidic glycosaminoglycans (AGAG) in the proteoglycans was determined enzymatically by digestion with chondroitinase-AC II, chondroitinase-ABC, Streptomyces, hyaluronidase and keratanase. Under both associative and dissociative conditions, uniform distribution of chondroitin sulfate (CS) isomers from proteoglycans of different ages was observed: With increasing age, the relative proportion of 4-sulfated disaccharide units in total AGAG decreased, whereas that of 6-sulfated disaccharide units increased. The relative proportion of 4-sulfated disaccharide units in total CS and the ratio of 4-sulfated disaccharide units to 6-sulfated disaccharide units were greater in arthritic cartilages than in normal cartilages of the same ages. At all three ages studied, the relative proportion of 4-sulfated disaccharide units in sequential fractions increased with the decrease of cesium chloride (CsC1) density, as the proportion of 6-sulfated disaccharide units decreased. The relative proportions of hyaluronic acid (HA) and keratan sulfate (KS) increased with age. The AGAG components of cartilage proteoglycans were distributed with a certain regularity in the fractions of CsCl density gradients, but underwent changes with increasing age and in arthritic process.

Topics: Aging; Animals; Arthritis; Arthritis, Experimental; Cartilage, Articular; Cattle; Chondroitin Sulfates; Disaccharides; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Hyaluronic Acid; Keratan Sulfate; Proteoglycans

The structure of chondroitin sulfates and proteoglycans extracted from human normal young and adult cartilages and also from human arthrosic cartilages are reported. The adult articular cartilage contains almost exclusively chondroitin 6-sulfate, whereas the normal young and the arthrosic cartilage chondroitin sulfates are hybrid polymers, containing 4-sulfated and 6-sulfated disaccharide units, distributed in a quite random way along the molecules. The young cartilage proteoglycans also differ from the adult cartilage proteoglycans by their contents of keratan sulfate, the relative proportion of nonaggregating proteoglycans and electrophoretic migration in agarose gel slabs. The proteoglycans from arthrosic cartilages are very similar to those from young normal cartilages. Such changes in composition could lead to alterations in the proportion and size of the aggregates they form in the cartilages, furnishing the conditions for the processes of growth and calcification to occur.

Topics: Arthritis; Cartilage; Chondroitin; Chondroitin Sulfates; Electrophoresis, Agar Gel; Humans; Infant; Middle Aged; Proteoglycans

Topics: Arthritis; Biological Transport; Cartilage, Articular; Chondroitin Sulfates; Humans; Synovial Fluid

Extracts of human peripheral blood polymorphonuclear leukocyte granules, and two purified proteases derived from such extracts, an elastase and a chymotrypsin-like enzyme, degrade isolated bovine nasal cartilage proteoglycan at neutral pH. Viscosity studies indicate that the leukocyte granule extracts lack hyaluronidase activity and that their degradative effect on proteoglycan at physiological pH is due entirely to proteolytic action. Sepharose 4B gel chromatography and SDS-polyacrylamide gel electrophoresis of proteoglycan fractions treated with leukocyte granule enzymes at pH 7.0 indicate that they degrade one of the proteoglycan link proteins, release a fragment from the hyaluronic acid-binding portion of the proteoglycan subunit core protein, and break down the remainder of the proteoglycan subunit molecule into peptide fragments with varying numbers of chondroitin sulfate chains. Immunodiffusion studies indicate that the antigenic determinants of the proteoglycan subunit core protein and the link proteins survive treatment with granule proteases. Similar degradation of human articular cartilage proteoglycan by granule neutral proteases can be presumed to occur, in view of the similarity of structure of human articular and bovine nasal cartilage proteoglycans. The release of granule enzymes in the course of neutrophil-mediated inflammation can thus result in the degradation of cartilage matrix proteoglycan, leading to cartilage destruction and joint injury.

Topics: Animals; Arthritis; Cartilage, Articular; Cattle; Chemical Phenomena; Chemistry; Chondroitin Sulfates; Chromatography, Gel; Chymotrypsin; Cytoplasmic Granules; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Glycosaminoglycans; Humans; Immunodiffusion; Joint Diseases; Leukocytes; Nasal Septum; Pancreatic Elastase; Proteoglycans; Sodium Dodecyl Sulfate; Viscosity

Topics: Arthritis; Arthritis, Rheumatoid; Chondroitin Sulfates; Female; Fructose-Bisphosphate Aldolase; Humans; Hyaluronic Acid; Immunoglobulins; Leukocyte Count; Male; Prednisolone; Synovial Fluid; Viscosity

Topics: Arthritis; Arthritis, Rheumatoid; Blood Proteins; Chondroitin; Chondroitin Sulfates; Humans; Lipids; Serum Globulins

Topics: Antibodies; Antigens; Arthritis; Arthritis, Rheumatoid; Chondroitin; Chondroitin Sulfates; Humans; Streptococcus