Markers of joint tissue turnover in joint fluids from hips with osteonecrosis of the femoral head.

Osteonecrosis of the femoral head often results in secondary osteoarthritis of the hip joint; however, the pathologic processes underlying the destruction of articular cartilage are not fully understood. Molecular markers in the hip joint fluids were measured to examine the changes in turnover of cartilage and other joint tissues. Marker data were related to clinical, radiological, and histopathological changes in the articular cartilage of the hip. Forty-five patients (median age: 43 years) were studied. The median time between the onset of symptoms and sampling of hip synovial fluid was 6 months. Aggrecan fragments, C-propeptide of type-II collagen, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1 levels in joint fluid were determined by immunoassay. Osteonecrosis of the femoral head was graded by radiology as minimal collapse of the femoral head (stage 2: 26 patients), severe collapse (stage 3: 15 patients), or severe collapse with osteoarthritis (stage 4: four patients). Histological changes of the articular cartilage, consistent with early-stage osteoarthritis, were evident at stage 3 and were more advanced at stage 4. The average concentrations of proteoglycan fragments and C-propeptide of type-II collagen were 207 (SD 182) microg/ml and 19.6 (SD 19.3) ng/ml, respectively. The average concentrations of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 were 177 (SD 291) nM and 23.0 (SD 9.9) nM, respectively. Measurable levels for all markers assayed were noted in the earliest stage of the disease, only a few months after the onset of symptoms and well before the appearance of radiological changes. Levels of matrix metalloproteinase-3 and molar ratios of matrix metalloproteinase-3/tissue inhibitor of metalloproteinases-1 were higher in early stage disease than in later stage disease.

Localization of carboxy-terminal type II procollagen peptide (pCOL-II-C) and type II collagen in the repair tissue of full-thickness articular cartilage defect.

It is well established that a full-thickness articular cartilage defect is repaired with a fibrocartilaginous tissue of which cells are derived from undifferentiated mesenchymal stem cells in the bone marrow. To characterize the repair tissue immunohistochemically, full-thickness defects were created in rabbit knee joints, and the repair tissues immunostained at 3, 6, and 12 weeks after surgery. Well characterized polyclonal antibody against carboxyterminal type II procollagen peptide (pCOL-II-C) and monoclonal antibody against type II collagen were used to evaluate the repair tissue with regard to the metabolism of type II collagen. Immunohistochemistry revealed that pCOL-II-C was localized in or around most of the repair cells obtained at 3 and 6 weeks after surgery, while type II collagen distributed mainly in the pericellular matrix of metaplastic round-shaped repair cells. The results suggest that the repair cells taken at the early stage of the repair process of the defect could originally have more activity of type II collagen synthesis.

Characterization of the cells in the repair tissue of full-thickness articular cartilage defects.

It is well established that a full-thickness articular cartilage defect is repaired with a fibrocartilaginous tissue, cells of which are derived from undifferentiated mesenchymal stem cells in the bone marrow. To characterize the repair cells biochemically, full-thickness defects were created in rabbit knee joints and the repair tissues taken at 3, 6, and 12 weeks after surgery. The repair cells were cultured and examined biochemically to investigate the effects of four exogenous growth factors with regard to the metabolism of type II collagen and proteoglycans. A significant increase of carboxy-terminal type II procollagen peptide production was observed in the conditional medium of the repair cells, especially taken at 6 weeks after surgery, in the presence of each growth factor. Glycosaminoglycan content was also increased and proteoglycan synthesis stimulated. The repair cells taken at the early stage of the repair process could originally have more activity of type II collagen synthesis, and the growth factors used could enhance the differentiation of the repair cells in vitro.

Suppression of matrix metalloproteinase-3 synthesis by interleukin-4 in human articular chondrocytes.

OBJECTIVE: To evaluate the effect of interleukin-4 (IL-4) on IL-1 induced matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) production by human articular chondrocytes. METHODS: Monolayer cell culture of chondrocytes was obtained from human articular cartilage from patella within 24 h after death. MMP-3 and TIMP-1 protein levels were determined by ELISA. MMP-3 activity was assayed as caseinase activity. Amounts of MMP-3 and TIMP-1 mRNA were measured by Northern blot analysis. RESULTS: IL-4 suppressed IL-1 stimulated MMP-3 protein and enzyme activity. Moreover, IL-4 suppressed IL-1 induced MMP-3 mRNA. In contrast, IL-4 did not alter the level of TIMP-1 protein and mRNA. CONCLUSION: IL-4 may be implicated as a protective mediator of joint destruction seen in inflammatory arthritis.

Synovial fluid concentrations of the C-propeptide of type II collagen correlate with body mass index in primary knee osteoarthritis.

OBJECTIVE: To explore in a cross sectional study in patients with primary knee osteoarthritis (OA) the relations between body mass index (BMI), disease stage, and the concentrations of a putative joint fluid marker of type II collagen synthesis, procollagen II C-propeptide. PATIENTS AND METHODS: The study included 142 patients with knee OA (median age 68, median BMI 24.1). OA was staged radiologically. The concentrations in synovial fluid of procollagen II C-propeptide were measured by a sandwich enzyme immunoassay. RESULTS: Joint fluid concentrations of procollagen II C-propeptide were increased in knees with OA (median 3.7 ng/ml), compared with published reference values for knees in healthy adult volunteers (median 1.3 ng/ml). The concentrations of procollagen II C-propeptide were independently related to both OA stage and BMI (r = 0.343, p < 0.0001 and r, = 0.253, p = 0.002, respectively). CONCLUSIONS: Joint fluid concentrations of this putative marker of collagen II synthesis are high in early and mid-stage OA, but decrease in end stage disease. In addition and for the first time it was shown that the concentrations in synovial fluid of procollagen II C-propeptide increase with increasing BMI in primary knee OA. The increased joint fluid values of this marker in patients with primary knee OA and a high BMI, may reflect increased rates of collagen synthesis in their joint cartilage and could relate to the previously shown increased risk for disease progression in such patients.

Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system.

Free radical scavenging activities of water-soluble extracts from some natural sources, health foods, and antioxidant substances were measured using the JES-FR30 JEOL spectrometer. The objective was to develop a standardized method whereby comparison could be made between the radical scavenging activities of complex mixtures. Scavenging of hydroxyl radical was determined using DMPO. Activity was calibrated using a standard material, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1), an analog of vitamin C and vitamin E which is water soluble and stable at room temperature. The order of greatest hydroxyl radical scavenging activity was green tea extract, pine bark extract (Pycnogenol), Ginkgo Biloba extract (EGb 761), a flavonoid blend of several fruit and vegetable extracts (GNLD), and Bio-Normalizer (Sun-O Corp). Activity was determined after treatment of samples with ascorbic acid oxidase. This treatment revealed the presence of ascorbate in some natural extracts and commercial preparations. The pine bark extract was the most heat resistant and had ascorbate-like activity in the preparations. Scavenging of superoxide anion was determined using the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and analyzed by comparison with a standard curve made with superoxide dismutase. Comparison of the water solubilized components of natural source antioxidants showed that filtrates fractionated using centrifuge type Millipore filter tubes (M.W. < 100,000; M.W. < 10,000) also had almost the same SOD-like activity. Samples were also treated with ascorbate oxidase or by heating (100 degrees C for 10 min). The order of activity, from greatest to least, was Ginkgo biloba extract EGb 761, pycnogenol, beta-catechin, tea and BioNormalizer.

Pseudo-synovial cyst arising at the pubic bone region and forming a large femoral-inguinal mass.

We describe a patient with rheumatoid arthritis who presented a large femoral-inguinal mass. The mass proved to be a synovial cyst-like structure communicating with rigid cystic lesions at the pubic bone. No obvious communication between the cystic lesions and the hip joint or bursae was seen by hip arthrogram or in surgery. Pathological examination of the cystic lesion at the pubic bone revealed infiltration of multiple rheumatoid nodules with marked fibrinoid necrosis into the bone, with synovium-like tissue on it. However, no synovial tissue was observed in the femoral-inguinal mass. These findings suggest that the femoral-inguinal mass was not a true synovial cyst but can be called a pseudo-synovial cyst arising at the pubic bone region.

[Levels of matrix metalloproteinase-3 and urokinase-type plasminogen activator in knee synovial fluids from patients with rheumatoid arthritis and osteoarthritis].

The objective of this study is to determine the levels of matrix metalloproteinase-3 (MMP-3) and urokinase-type plasminogen activator (uPA) in knee synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Knee synovial fluids were collected from patients with RA and OA. Concentrations of MMP-3 were determined by enzyme immunoassay using a pair of monoclonal antibodies against human proMMP-3, and activities of uPA were measured by immunocapture assay using a polyclonal antiserum against human uPA. The median concentration of MMP-3 in synovial fluids was 97.5 +/- 82.6 micrograms/ml (range 1.06-336 micrograms/ml) for RA group and 20.5 +/- 11.3 micrograms/ml (range 6.19-42.8 micrograms/ml) for OA group. Levels of MMP-3 were significantly higher in RA group than in OA group. The median activity of uPA in synovial fluids was 0.053 +/- 0.052 i.u./ml (range 0.003-0.187 i.u./ml) for RA group and 0.072 +/- 0.059 i.u./ml (range 0.006-0.169 i.u./ml) for OA group. No significant difference of uPA activity was observed between RA and OA group. Significant correlation of the levels of MMP-3 with those of uPA was observed in RA group, however not in OA group. The increased levels of MMP-3 in synovial fluids in RA group may reflect an elevated matrix degrading activity due to joint inflammation. The significant correlation of MMP-3 with uPA in RA group suggests that MMP-3 could degrade cartilage matrix more actively in conjunction with PA-plasmin system than MMP-3 alone.

[Levels of chondroitin 4-sulfate, chondroitin 6-sulfate and carboxy-terminal type II procollagen peptide in knee synovial fluid after injury to the anterior cruciate ligament].

Changes in the metabolism of articular cartilage associated with injury to the anterior cruciate ligament (ACL) is known to be one of the important factors for the progression to secondary osteoarthritis. To investigate the efficacy of biochemical markers for monitoring the cartilage metabolism after injury to ACL, we measured the levels of chondroitin 4-sulfate (C-4S), chondroitin 6-sulfate (C-6S) and carboxy-terminal type II procollagen peptide (pCOL II-C) in knee synovial fluid (SF) from the patients with ACL rupture and compared with those in knee osteoarthritis (OA). Within 10 days after ACL rupture, levels of C-6S and C-4S in SF were significantly higher than those in early stage of OA. Both levels decreased gradually and became to the same levels as those in early stage of OA at 30 days after the injury. In contrast, pCOL II-C levels in SF just after the injury were observed to be lower than those in early stage of OA. Then they increased gradually to the levels of those in early stage of OA at 30 days after the injury. High levels of C-6S and C-4S in SF just after ACL rupture seemed to reflect the increased release of matrix fragments caused by cartilage destruction associated with the injury. pCOL II-C levels in SF seemed to reflect the repairing process that increased slowly after the cartilage destruction. Measurement of these cartilage derived macromolecules in SF could be useful tools for monitoring the metabolism in articular cartilage after injury.

Effects of indomethacin on the production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 by human articular chondrocytes.

OBJECTIVE: To study the action of indomethacin on cartilage catabolic activity by comparing the production of a matrix degrading proteinase and its inhibitor in human articular chondrocyte cultures. METHODS: Matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in conditioned medium from human articular chondrocyte cultures were measured using a one-step sandwich enzyme immunoassay. TIMP-1 mRNA expression was analyzed by Northern blotting using a 0.6 kb cDNA probe for human TIMP-1. RESULTS: Human recombinant interleukin 1 beta (IL-1 beta) increased MMP-3 levels in primary chondrocyte cultures. Indomethacin at 10(-5) M inhibited this IL-1 beta stimulation, but had no effect in the therapeutic range (10(-6)-10(-7) M). Low levels of indomethacin (10(-7) M) significantly increased the production of TIMP-1 by chondrocytes. Synthesis of TIMP-1 appeared to be inhibited by prostaglandin E2 (PGE2), since exogenously added PGE2 reversed the stimulating effect of indomethacin on TIMP-1 production. Northern blot analysis showed that 10(-7) M indomethacin increased TIMP-1 mRNA levels in chondrocytes. CONCLUSION: Our findings indicate that low levels of indomethacin can benefit matrix metabolism by affecting the balance of proteinases to their inhibitors in human articular cartilage.

Procollagen II C-propeptide in joint fluid: changes in concentration with age, time after knee injury, and osteoarthritis.

OBJECTIVE: To determine in a cross sectional study the concentrations in joint fluid of the C-propeptide of collagen II (pCol II-C) in patients with knee injury and developing osteoarthritis (OA). METHODS: Synovial fluid (SF) samples were collected from knees of healthy volunteers, from patients with injury to the knee causing lesions of the anterior cruciate ligament and/or menisci, and from patients with posttraumatic or primary OA. Concentrations of pCol II-C were determined by enzyme immunoassay with a polyclonal antiserum against the bovine propeptide. RESULTS: The median concentration of pCol II-C in joint fluid in the reference group was 1.3 ng/ml (range 0.1-5.7 ng/ml). Median concentrations of pCol II-C in joint fluid were increased 2-4-fold in all 3 study groups over that in the reference group. Very high concentrations of propeptide were noted in samples from patients younger than about 18 years. Propeptide concentrations were increased after knee injury, with a suggested peak at about 1-4 years evident for patients with cruciate ligament injury. pCol II-C levels were increased at all stages of OA development, except in the most advanced phases. CONCLUSION: The increased levels of pCol II-C in SF may reflect an increased rate of synthesis of collagen II in the joint cartilage of patients with knee injury and developing OA. The increase reaches a maximum well before radiographic changes indicative of OA are apparent, and occurs during a disease phase characterized by signs of increased degradation of collagen II, aggrecan, and other matrix components. Further studies of markers of matrix metabolism of cartilage, bone, and other joint tissues in human and animal models of OA may aid in the identification of process markers, individuals at risk, and new therapeutic targets.

The superficial layer of human articular cartilage is more susceptible to interleukin-1-induced damage than the deeper layers.

OBJECTIVE: To compare the responses of chondrocytes from superficial and deep layers of normal human articular cartilage to interleukin-1 (IL-1) and IL-1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL-1 on these cells. METHODS: Cartilage and chondrocytes from superficial and deeper layers of human femoral condyles were cultured with and without IL-1 in the presence and absence of IRAP. The effect of these agents on 35S- proteoglycan synthesis and catabolism and production of stromelysin and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by biochemical and immunologic assays. Receptor binding was evaluated using 125I-labeled IL-1. RESULTS: IL-1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP-l:stromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL-1 more effectively in chondrocytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high-affinity b!nding sites for IL-1 as did cells from deep cartilage. CONCLUSION: Chondrocytes from the surface of articular cartilage show a greater vulnerability to the harmful effects of IL-1 and are less responsive to the potential therapeutic effects of IRAP than cells in the deeper layers of the tissue.

Markers of cartilage matrix metabolism in human joint fluid and serum: the effect of exercise.

The concentrations of cartilage proteoglycan (aggrecan), stromelysin-1, tissue inhibitor of metalloproteinases-1 (TIMP-1) and procollagen II C-propeptide in knee joint fluid and the levels of aggrecan, hyaluronan and keratan sulfate in serum were measured before and after exercise in 33 healthy athletes. The samples before exercise were obtained after 24 h rest from running or soccer and the samples after exercise were obtained 30-60 min after the exercise. Nine athletes ran on a treadmill for 60 min, 16 ran on road for 80 min and 8 played one soccer game (90 min). A reference group of 28 patients with knee pain but not evidence of joint pathology or injury was used for comparison. In joint fluid no single marker from the degradative processes in cartilage matrix changed significantly with exercise but all showed a rising trend. All markers except stromelysin showed lower concentrations in athletes at rest compared to the reference group. In serum from runners before exercise the concentration of keratan sulfate was significantly higher than in both the soccer and reference groups and further increased after exercise. The increase in markers after exercise may reflect an effect of mechanical loading in combination with a possible high turnover rate of body cartilage matrix in these individuals.

Significance of the levels of carboxy terminal type II procollagen peptide, chondroitin sulfate isomers, tissue inhibitor of metalloproteinases, and metalloproteinases in osteoarthritis joint fluid.

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.

Intra-articular hyaluronic acid in osteoarthritis of the knee: an investigation into mechanisms of action.

The objective of this study was to investigate mechanisms of action of intra-articular hyaluronic acid in osteoarthritis (OA) of the knee. Twelve patients with bilateral knee OA and synovial effusions entered a randomized, single-blind, blind observer study. Hyaluronic acid ("Hyalgan", Fidia SpA, Italy) or placebo were given by intra-articular injection weekly for 5 weeks. Assessments included clinical indices and imaging (magnetic resonance imaging (MRI) and 99m Tc bone scanning) before and after the course of injections. In addition, synovial fluid keratan sulfate (KS), chondroitin sulfate (CS) and C-propeptide of type II collagen (CPII) were measured. MRI and 99m Tc scanning showed no change in either treated or placebo knees over the 6-week study period. A fall in KS levels occurred in treated knees compared with placebo (Wilcoxon paired test, P = 0.1), although this did not reach significance perhaps due to small sample numbers). Ten out of 12 treated knees showed a fall in KS, compared with four out of 12 placebo knees. CS and CPII levels did not change significantly. Intra-articular injection of hyaluronic acid did not result in any improvement in the clinical indices compared to the placebo. In conclusion, assessment of cartilage markers may be of value when studying novel therapies in OA. MRI appearances remain remarkably stable over a 6-week period.

Body fluid markers of cartilage changes in osteoarthritis.

Various markers of the metabolism of articular cartilage have been identified in synovial fluid, blood, and urine of patients with osteoarthritis (OA). The joint fluid level of a cartilage-derived molecule, or its fragment, can be used as a marker of the synthesis or catabolism of that molecule in the articular surfaces within that joint. In blood and urine, on the other hand, the level of a marker is useful in assessing systemic changes affecting the metabolism of a molecule in all the cartilages in the body. Quantification of specific markers in body fluids already has proved useful in identifying increased catabolic as well as anabolic activities in articular cartilage during preradiologic as well as later stages of OA. The markers also can be sued for monitoring the effect of drugs on cartilage matrix molecules and in differentiating among different subtypes of osteoarthritis. Markers should prove most useful in prospective studies aimed at identifying early changes in cartilage metabolism in humans at high risk for developing OA.

Joint fluid carboxy-terminal type II procollagen peptide as a marker of cartilage collagen biosynthesis.

Joint fluid levels of carboxy-terminal type II procollagen peptide (pCOL II-C) were measured in osteoarthritis, rheumatoid arthritis and traumatic arthritis by a newly developed one-step enzyme immunoassay (EIA). The detection limit of the new method was as low as 0.2 ng/ml. The levels of pCOL II-C were significantly (P < 0.001) higher in osteoarthritis and traumatic arthritis than in rheumatoid arthritis. In osteoarthritis, pCOL II-C levels were higher in moderately afflicted patients. Since type II collagen is a unique component of cartilage, pCOL II-C levels in joint fluids could reflect the synthetic activity of type II collagen of chondrocytes in the diseased joint and therefore could be utilized as a simple marker of type II collagen synthesis in articular cartilage in joint diseases.

Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines.

OBJECTIVE: To investigate the effects of hyaluronic acid (HA) on the release of proteoglycan by cultured rabbit chondrocytes. METHODS: Articular cartilage chondrocytes were isolated from the knee joints of New Zealand white rabbits. Proteoglycan synthesis after incubation with HA was determined by measuring 35S-sulfate incorporation. Cells incubated with HA were labeled with 3H-glucosamine and applied to a Sepharose CL-2B column. After incubation of confluent cells with 35S-sulfate and then with HA in various concentrations in the presence or absence of cytokines, proteoglycan release from the cell matrix layer was measured. RESULTS: HA (M(r) 3 x 10(5) to 19 x 10(5)), at 10 micrograms/ml to 1 mg/ml, had little effect on the incorporation of 35S-sulfate or 3H-glucosamine into cartilage matrix proteoglycans, or on the hydrodynamic size of proteoglycan monomers, in rabbit chondrocyte cultures. However, at 10-1,000 micrograms/ml, HA suppressed the release of 35S-proteoglycans from the cell matrix layer into the medium in the presence and absence of interleukin-1, tumor necrosis factor alpha, or basic fibroblast growth factor. CONCLUSION: These results suggest that HA is a potent inhibitor of the displacement of matrix proteoglycan into culture medium.

Quantitation of chondroitin 4-sulfate and chondroitin 6-sulfate in pathologic joint fluid.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Clinical usefulness of the measurement of type-II procollagen carboxypeptide (C-II propeptide, pColl-II-C) in synovial fluid as a marker of collagen metabolism in cartilage].

Type-II procollagen-C-peptide (pColl-II-C) in synovial fluids was studied in 319 patients with osteoarthritis (OA; 151), rheumatoid arthritis (RA; 141), traumatic arthritis (TA; 27) and 15 healthy volunteers using the newly developed ELISA kit. The mean levels of pColl-II-C in synovial fluids of healthy controls, OA, TA, and RA were 0.3 +/- 0.1 ng/ml, 5.9 +/- 0.3 ng/ml, 6.8 +/- 1.4 ng/ml and 1.1 +/- 0.1 ng/ml, respectively. pColl-II-C levels in synovial fluids of OA and TA were significantly higher compared to those of healthy controls and RA. It was also demonstrated that pColl-II-C levels could reflect the quantitative and qualitative change of cartilage metabolism. Therefore, the quantification of this molecule in synovial fluid could be beneficial to know the synthetic activity of type II collagen of chondrocytes, since pColl-II-C is a part of the precursor molecule of type II collagen.