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At least 793 records · Page 44Linked to original sources
PubMed2003

Involvement of CD44 in induction of matrix metalloproteinases by a COOH-terminal heparin-binding fragment of fibronectin in human articular cartilage in culture.

OBJECTIVE: To investigate the mechanism of induction of matrix metalloproteinases (MMPs) by a 40-kd COOH-terminal heparin-binding fibronectin fragment (HBFN-f) containing III12-14 and IIICS domains in human articular cartilage in culture. METHODS: Human articular cartilage was removed from macroscopically normal femoral heads and cultured with HBFN-f. MMP secretion into conditioned media was analyzed by immunoblotting (MMPs 1 and 13) and by gelatin zymography (MMPs 2 and 9). Type II collagen cleavage by collagenase was monitored in culture by immunoassay. Involvement of specific peptide-binding domains in HBFN-f and the involvement of CD44 were assessed with synthetic peptides and an anti-CD44 antibody. Immunofluorescence histochemistry was performed using fluorescein isothiocyanate-conjugated anti-CD44 antibody. RESULTS: HBFN-f stimulated production of MMPs 1, 2, 9, and 13 in association with type II collagen cleavage by collagenase in human articular cartilage. Peptide V (WQPPRARI) of HBFN-f, which can bind cell surface heparan sulfate proteoglycan (HSPG), blocked MMP induction by HBFN-f, while the scrambled peptide V (RPQIPWAR) had no effect. Peptide CS-1 of 25 amino acids in IIICS of HBFN-f caused no significant effect. Treatment of cartilage with anti-CD44 antibody or HSPG resulted in significant inhibition of HBFN-f-stimulated MMP production. Preincubation with peptide V blocked binding of the anti-CD44 antibody to chondrocytes in cartilage. CONCLUSION: Interaction of the peptide V sequence in HBFN-f with glycosaminoglycans, such as those in CD44, plays an important role in HBFN-f-stimulated MMP production in articular cartilage. Because CD44 is up-regulated in osteoarthritic and rheumatoid arthritic cartilage, the role of the interaction between CD44 and HBFN-f in these pathologies should be of relevance and should be studied further.

Carrier Proteins↗
PubMed2000

Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis.

A bovine cartilage explant system was used to evaluate the effects of injurious compression on chondrocyte apoptosis and matrix biochemical and biomechanical properties within intact cartilage. Disks of newborn bovine articular cartilage were compressed in vitro to various peak stress levels and chondrocyte apoptotic cell death, tissue biomechanical properties, tissue swelling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocyte apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was maximal by 24 h after the termination of the loading protocol. At high peak stresses (>20 MPa), greater than 50% of cells apoptosed. When measured in uniaxial confined compression, the equilibrium and dynamic stiffness of explants decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress. In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased significantly after injurious stresses of 12 and 7 MPa, respectively. Together, these results suggested that injurious compression caused a degradation of the collagen fibril network in the 7- to 12-MPa range. Consistent with this hypothesis, injurious compression caused a dose-dependent increase in tissue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were also released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injurious compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is currently unclear whether this initial cellular response subsequently drives cartilage matrix degradation and changes in the biomechanical properties of the tissue.

Animals↗
PubMed1996

Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants.

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articular cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated. Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism.

Animals↗
PubMed2006

Expression of extracellular matrix molecules typical of articular cartilage in the human scapholunate interosseous ligament.

The scapholunate interosseous ligament (SLIL) connects the scaphoid and lunate bones and plays a crucial role in carpal kinematics. Its rupture leads to carpal instability and impairment of radiocarpal joint function. As the ligament is one of the first structures affected in rheumatoid arthritis, we conducted an immunohistochemical study of cadaveric tissue to determine whether it contains known autoantigens for rheumatoid arthritis. We immunolabelled the ligament from one hand in 12 cadavers with monoclonal antibodies directed against a wide range of extracellular matrix (ECM) molecules associated with both fibrous and cartilaginous tissues. The labelling profile has also enabled us to comment on how the molecular composition of the ligament relates to its mechanical function. All regions of the ligament labelled for types I, III and VI collagens, chondroitin 4 and 6 sulphates, keratan sulphate, dermatan sulphate, versican, tenascin and cartilage oligomeric matrix protein (COMP). However, both entheses labelled strongly for type II collagen, aggrecan and link protein and were distinctly fibrocartilaginous. In some regions, the ligament attached to bone via a region of hyaline cartilage that was continuous with articular cartilage. Labelling for cartilage molecules in the midsubstance was most evident dorsally. We conclude that the SLIL has an ECM which is typical of other highly fibrocartilaginous ligaments that experience both tensile load and shear. The presence of aggrecan, link protein, COMP and type II collagen could explain why the ligament may be a target for autoantigenic destruction in some forms of rheumatoid arthritis.

Aged↗
PubMed2002

Horizontally oriented clusters of multiple chondrons in the superficial zone of ankle, but not knee articular cartilage.

Osteoarthritis is a progressive disease that is initiated at the surface of articular cartilage and proceeds to destroy the entire depth of the cartilage. The prevalence of osteoarthritis varies in different joints; e.g., the ankle joint has a very low prevalence of the disease compared to the knee joint. To better understand any inherent differences between the articular cartilage of the ankle and that of the knee that would account for the difference in occurrence of osteoarthritis, studies were undertaken to examine differences between the superficial zones in these two joint cartilages obtained from human donors. Chondrocytes in the superficial zones of the normal ankle (talocrural) and the normal knee (tibiofemoral) joints were identified with a monoclonal antibody specific for the superficial zone protein (SZP). When the chondrocytes from both joints were compared in serial horizontal sections, the chondrocytes in the superficial zone of the knee cartilage were seen either as isolated single cells or as doublets. However, the chondrocytes within the superficial zone of normal ankle cartilage were arranged in planar clusters containing multiple chondrons composed of 2-13 cells. There were no detectable differences in the chondrocyte clusters in the superficial zone of the ankle with respect to age, gender, or site on the cartilage surface. Adjacent to a lesion in an ankle joint with degenerative changes, the clusters were larger, containing up to 22 chondrocytes. This is the first report documenting the presence of multiple chondrons in the superficial zone of normal human adult articular cartilage.

Adolescent↗
PubMed1994

Continuous passive motion stimulates repair of rabbit knee articular cartilage after matrix proteoglycan loss.

Continuous passive motion facilitates repair of full-thickness defects in the articular cartilage in rabbits. Studies were conducted to determine whether continuous passive motion would similarly affect the repair process after injection of chymopapain into the rabbit knee. Adolescent rabbits were injected with chymopapain and then given intermittent active motion in the form of free cage activity or continuous passive motion of the injected knee. After injection of either 0.2 or 2 mg chymopapain into the knee, serum keratan sulfate levels rose sharply, indicating proteoglycan loss, and, in all cases, peaked at 24 hours between 200-800% of preinjection levels. Importantly, serum keratan sulfate levels were significantly elevated within 1 hour when joints were submitted to immediate continuous passive motion after the injection. As shown previously, injection of either 0.2 or 2 mg chymopapain into the knee, followed by intermittent active motion, resulted in a pronounced loss of proteoglycans by Day 2, partial restoration of proteoglycans by Day 9, continued proteoglycan synthesis by Day 21 in animals receiving the lower dose, and severe degenerative changes by Day 21 in animals receiving the higher dose. In all animals that received either high or low doses of chymopapain, as well as 2 days of intermittent active motion and then continuous passive motion, the articular cartilage surface was intact by Day 9, and replenishment of proteoglycans had occurred in pericellular and interterritorial areas. By Day 21, the surface of the articular cartilage was still intact, and replenishment of proteoglycans in loaded regions continued in all animals receiving either dose of chymopapain. These results indicate that a period of intermittent active motion followed by continuous passive motion of a chymopapain injected knee may protect and stimulate repair of the articular cartilage matrix after chymopapain-induced injury.

Animals↗
PubMed1996

Precision of sonographic measurement of articular cartilage: inter- and intraobserver analysis.

OBJECTIVE: To establish the precision of sonographic measurement of the thickness of the articular cartilage of the hip and knee in children. DESIGN: The precision was assessed by evaluating the intra- and interobserver variations in sonographic measurements. PATIENTS: A total of 65 healthy children were in the study. The articular cartilage of the right hip and knee of 40 subjects (mean age 10.3 years, range 4-16.9 years) was evaluated in masked fashion by two observers to assess the interobserver variability. The articular cartilage of the right hip and knee of 25 children (mean age 10.4 years, range 6.2-15.5 years) was examined twice by the same observer to assess the intraobserver variability. RESULTS AND CONCLUSIONS: Discrepancies between repeated measurements were expressed as data differences. The "limits of agreement" of data differences, i.e. the mean +2 SD and the mean -2 SD, ranged from -0.26 to +0.22 mm and from -0.56 to +0.48 mm for the interobserver analysis of the femoral head cartilage (FHC) and femoral condylar cartilage (FCC), respectively. The "limits of agreement" for the intraobserver analysis ranged from -0.16 to +0.15 mm and from -0.51 to +0.41 mm for the FHC and the FCC, respectively. The overall precision of the sonographic measurements was satisfactory. When used for determination of skeletal age, sonographic assessment of FHC thickness resulted in under/overestimation of skeletal age by about 7.5 months. In conclusion, sonographic measurement of articular cartilage is precise enough to be used in clinical practice.

Age Determination by Skeleton↗
PubMed1999

[Autologous osteo-chondral grafts in the management of articular cartilage lesions].

UNLABELLED: It is well known that the capacity of articular cartilage for repair is limited. There have been many attempts to address this problem. However, treatment options are limited and the long-term outcome is uncertain. This article will focus on the osteochondral autograft transplantation (OAT), which is currently the only surgical cartilage repair technique that provides and retains proper hyaline articular cartilage. Osteochondral autograft transplants have been associated with a good rate of success, but further long-term follow-up and biomechanical evaluation are essential. LIMITATIONS: size and depth of osteochondral defects, availability of donor autologous grafts, potential for damaging donor sites, the dead spaces between circular grafts and integration of donor and recipient hyaline cartilage.

Bone Transplantation↗
PubMed1988

Chondrocyte distribution in the articular cartilage of human femoral condyles.

The distribution of chondrocytes throughout the total thickness of articular cartilage from the femoral condyles of infants, children and adults has been studied using serial sections cut parallel as well as perpendicular to the articular surface. The thickness of the articular cartilage was estimated in fixed sections. In one of the adult specimens, the thickness of the articular cartilage was estimated firstly by direct measurement of the cut surfaces of a series of blocks cut from both condyles and then from the number of parallel sections of the cartilage prepared from those blocks. Cell density was highest in the superficial zone of all specimens examined, declining to lower values in the deep zone of the cartilage. Within this pattern the infant specimens had the highest values for cell density and the adults the lowest, with values for children in an intermediate range. There was no significant variation in cell density across the condyles of the selected adult specimen. The absolute values for cartilage thickness depended on the method used, but in general total thickness was found to approximately double from late gestation to maturity. In the selected adult specimen, the cartilage was thickest just anterior and posterior to the main weight-bearing area of the condyles.

Adult↗
PubMed2006

Chondroitin sulfate reduces the friction coefficient of articular cartilage.

The objective of this study was to investigate the effect of chondroitin sulfate (CS)-C on the frictional response of bovine articular cartilage. The main hypothesis is that CS decreases the friction coefficient of articular cartilage. Corollary hypotheses are that viscosity and osmotic pressure are not the mechanisms that mediate the reduction in the friction coefficient by CS. In Experiment 1, bovine articular cartilage samples (n=29) were tested in either phosphate buffered saline (PBS) or in PBS containing 100mg/ml of CS following 48h incubation in PBS or in PBS+100mg/ml CS (control specimens were not subjected to any incubation). In Experiment 2, samples (n=23) were tested in four different solutions: PBS, PBS+100mg/ml CS, and PBS+polyethylene glycol (PEG) (133 or 170mg/ml). In Experiment 3, samples (n=18) were tested in three solutions of CS (0, 10 and 100mg/ml). Frictional tests (cartilage-on-glass) were performed under constant stress (0.5MPa) for 3600s and the time-dependent friction coefficient was measured. Samples incubated or tested in a 100mg/ml CS solution exhibited a significantly lower equilibrium friction coefficient than the respective PBS control. PEG solutions delayed the rise in the friction coefficient relative to the PBS control, but did not reduce the equilibrium value. Testing in PBS+10mg/ml of CS did not cause any significant decrease in the friction coefficient. In conclusion, CS at a concentration of 100mg/ml significantly reduces the friction coefficient of bovine articular cartilage and this mechanism is neither mediated by viscosity nor osmolarity. These results suggest that direct injection of CS into the joint may provide beneficial tribological effects.

Animals↗
PubMed2006

Articular cartilage MR imaging and thickness mapping of a loaded knee joint before and after meniscectomy.

OBJECTIVE: We describe a technique to axially compress a sheep knee joint in an MRI scanner and measure articular cartilage deformation. As an initial application, tibial articular cartilage deformation patterns after 2 h of static loading before and after medial meniscectomy are compared. METHODS: Precision was established for repeated scans and repeated segmentations. Accuracy was established by comparing to micro-CT measurements. Four sheep knees were then imaged unloaded, and while statically loaded for 2 h at 1.5 times body weight before and after medial meniscectomy. Images were obtained using a 3D gradient echo sequence in a 4.7 T MRI. Corresponding 3D cartilage thickness models were created. Nominal strain patterns for the intact and meniscectomized conditions were compared. RESULTS: Coefficients of variation were all 2% or less. Root mean squared errors of MR cartilage thickness measurements averaged less than 0.09 mm. Meniscectomy resulted in a 60% decrease in the contact area (P=0.001) and a 13% increase in maximum cartilage deformation (P=0.01). Following meniscectomy, there were greater areas of articular cartilage experiencing abnormally high and low nominal strains. Areas of moderate nominal strain were reduced. CONCLUSIONS: Medial meniscectomy resulted in increased medial tibial cartilage nominal strains centrally and decreased strains peripherally. Areas of abnormally high nominal strain following meniscectomy correlated with areas that are known to develop fibrillation and softening 16 weeks after medial meniscectomy. Areas of abnormally low nominal strain correlated with areas of osteophyte formation. Studies of articular cartilage deformation may prove useful in elucidating the mechanical etiology of osteoarthritis.

Animals↗
PubMed2001

High-efficiency non-viral transfection of primary chondrocytes and perichondrial cells for ex-vivo gene therapy to repair articular cartilage defects.

BACKGROUND: Primary perichondrial cells and chondrocytes have been used to repair articular cartilage defects in tissue engineering studies involving various animal models. Transfection of these cells with a gene that induces chondrocytic phenotype may form an ideal method to affect tissue engineering of articular cartilage. DESIGN: A protocol for high-efficiency transfection of primary perichondrial and cartilage cells was optimized. Plasmids carrying the marker beta-galactosidase (beta-gal), PTHrP and TGF-beta1 genes driven by a strong mammalian promoter were transfected into primary perichondrial cells and chondrocytes. A three-step method was used to achieve high efficiency of transfection: (1) permeabilization of primary cells using a mild detergent, (2) association of plasmid DNAs with a polycationic (poly-l-lysine) core covalently linked to a receptor ligand (transferrin), (3) introduction of cationic liposomes to form the quaternary complex. For in-vivo assessment, polylactic acid (PLA) scaffolds seeded with beta-gal transfected perichondrial cells were implanted into experimentally created osteochondral defects in rabbit knees for 1 week. RESULTS: The efficiency of transfection was determined to be over 70%in vitro. The transformed cells continued to express beta-gal, in vivo for the entire test period of 7 days. Furthermore, primary perichondrial cells transfected with TGF-beta1 and PTHrP over-expressed their cognate gene products. CONCLUSION: The ability to transfect autologous primary perichondrial cells and chondrocytes with high efficiency using a non-viral system may form a first step towards tissue engineering with these transformed cells to repair articular cartilage defects.

Animals↗
PubMed1989

Frictional response of articular cartilage containing crystals.

Many joint diseases are associated with the deposition of crystals in articular cartilage. Three main types are commonly found: calcium pyrophosphate, calcium hydroxyapatite and monosodium urate. The effects of these articular crystals on the frictional properties and the surface condition of the articular cartilage were studied. A total of 43 cartilage specimens cut from 19 post-mortem knee joints have been tested in purpose-designed apparatus. The results show that a high friction coefficient and a high level of crystal deposition tend to occur with a worsening of the surface quality of the articular cartilage.

Biocompatible Materials↗
PubMed1989

Retardation of articular cartilage degradation by glycosaminoglycan polysulfate, pentosan polysulfate, and DH-40J in the rat air pouch model.

The rat subcutaneous air pouch model was adapted to examine the in vivo degradation of implanted rabbit articular cartilage, both with and without induced air pouch inflammation, over a 7-day period. The effects of 3 drugs, glycosaminoglycan polysulfate (Arteparon), pentosan polysulfate (SP-54), and zinc-chelated pentosan polysulfate (DH-40J), on inflammation-induced cartilage degradation were also examined. Implanted articular cartilage from noninflamed air pouches showed a reduction in total proteoglycan (PG) content (as hexuronic acid), but not in PG extractability or aggregation, compared with cartilage maintained in tissue culture. The injection of peptone into the air pouch as an inflammogen caused an influx of leukocytes and plasma exudate and a reduction in implanted articular cartilage PG content, extractability, and aggregation, which was significantly greater than that which occurred in noninflamed air pouches. In vitro experiments demonstrated that peptone did not have a direct effect on cartilage PG degradation. Daily injection of Arteparon, SP-54, or DH-40J (10 mg/kg) into peptone-inflamed air pouches significantly increased the PG content, extractability, and aggregation in implanted articular cartilage, compared with that in cartilage from non-drug-treated control animals. The infiltration of leukocytes into the peptone-inflamed air pouches was significantly reduced by daily administration of Arteparon, 10 mg/kg. At an equivalent dose, DH-40J increased leukocyte numbers in the pouch fluid, whereas SP-54 had no significant effect on leukocyte accumulation.

Animals↗
PubMed1995

An assay for galactosyltransferase-I activity in articular cartilage.

UDP-D-Galactose:D-xylose galactosyltransferase (Galactosyltransferase-I) is an enzyme involved in the synthesis of the linkage region of chondroitin sulfate. Measurement of galactosyltransferase-I in mature articular cartilage has depended on milling such tissue in liquid nitrogen to break open the cells and enable interaction of exogenous substrates with galactosyltransferase-I. This process requires large amounts (approximately 1 g wet wt) of cartilage. This paper reports the development of an assay for galactosyltransferase-I in articular cartilage where 10-25 mg (wet wt) of the tissue was extracted with a buffer containing the detergent Thesit. This assay was more time efficient, required less tissue, and was linear for up to 6 h. It was effective on both mature bovine articular cartilage and embryonic chick epiphyseal cartilage, detecting 100 and 68% of total galactosyltransferase-I activity, respectively. The higher number of measurements available allowed kinetic studies to be conducted on bovine articular cartilage explant cultures under conditions of up- and down-regulation. Incubation with fetal calf serum resulted in an increase in galactosyltransferase-I activity. Galactosyltransferase-I activity, however, did not change markedly in cartilage cultured in the absence of fetal calf serum or in the presence of cycloheximide. A soluble preparation of galactosyltransferase-I, extracted from bovine articular cartilage using Thesit, eluted from a Superose-6 column, with a molecular mass of about 55 kDa.

Animals↗
PubMed2005

Age-related changes in the expression of gelatinase and tissue inhibitor of metalloproteinase genes in mandibular condylar, growth plate, and articular cartilage in rats.

Mandibular condylar cartilage acts as both articular and growth plate cartilage during growth, and then becomes articular cartilage after growth is complete. Cartilaginous extracellular matrix is remodeled continuously via a combination of production, degradation by matrix metalloproteinases (MMPs), and inhibition of MMP activity by tissue inhibitors of metalloproteinases (TIMPs). This study attempted to clarify the age-related changes in the mRNA expression patterns of MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 in mandibular condylar cartilage in comparison to tibial growth plate and articular cartilage using an in situ hybridization method in growing and adult rats. MMP-2 and MMP-9 were expressed in a wide range of condylar cartilage cells during growth, and their expression domains became limited to mature chondrocytes in adults. The patterns of TIMP-1 and TIMP-2 expression were similar to those of MMP-2 and MMP-9 during growth, and were maintained until adulthood. TIMP-3 was localized to hypertrophic chondrocytes throughout the growth stage. Therefore, we concluded that TIMP-1 and TIMP-2 were general inhibitors of MMP-2 and MMP-9 in condylar cartilage, while TIMP-3 regulates the collagenolytic degradation of the hypertrophic cartilage matrix.

Aging↗
PubMed1987

Low molecular mass trypsin inhibitors in normal and osteoarthritic human articular cartilage.

A modified radial diffusion assay was used for the direct semiquantitative determination of low molecular mass trypsin inhibitors in small samples of human cartilage. The low molecular mass trypsin inhibitor in articular cartilage of normal human femoral heads is not distributed evenly but occurs in areas of low, medium and high content. The weight-bearing area of the femoral head belongs among the regions with low inhibitor content. The results obtained with osteoarthritic femoral heads showed that the inhibitor content in osteoarthritic cartilage is significantly lower than that in normal articular cartilage (p less than 0.1%).

Adult↗
PubMedDate not supplied

The stimulation of mononuclear cells from patients with rheumatoid arthritis to degrade articular cartilage is not modulated by cartilage itself.

OBJECTIVE: To study the modulation of mononuclear cell (MNC) activity in patients with rheumatoid arthritis (RA) by constituents released from human articular cartilage, which may be present in vivo during early events of the disease, when articular cartilage is not only mildly damaged. METHODS: In an attempt to stimulate RA MNC, cells were co-cultured with healthy or mildly damaged articular cartilage tissue. In addition, because of the reported cross-reactivity between cartilage constituents and mycobacterial heat-shock protein (hsp60), RA MNC sensitized with hsp60 were also co-cultured with cartilage tissue. Activation of the RA MNC was assessed by analysing the production of catabolic factors involved in joint damage. For this purpose culture supernatants of the treated RA MNC, comprising the catabolic factors, were added to freshly isolated articular cartilage explants. As a read out for catabolic activity, proteoglycan (PG) turnover by the explants was determined. RESULTS: Spontaneous activity of untreated RA MNC caused inhibition of PG synthesis and increased PG release upon addition of their culture supernatants to the cartilage explants. This MNC activity was not enhanced by the constituents released from healthy or mildly damaged cartilage tissue, whereas sensitization of RA MNC with hsp60 resulted in a 40% enhanced inhibition of PG synthesis. However, even under these pre-activated conditions no reactivity towards the cartilage constituents could be observed. CONCLUSION: Cartilage constituents released from mildly damaged cartilage tissue, as may be present during the early events of RA. do not modulate the catabolic activity of RA MNC.

Adult↗