REGULATION OF CARTILAGE OLIGOMERIC MATRIX PROTEIN-SYNTHESIS IN HUMAN SYNOVIAL-CELLS AND ARTICULAR CHONDROCYTES

Objective. Cartilage oligomeric matrix protein (COMP) is a component o f the extracellular matrix of articular cartilage, Its increased prese nce in synovial fluid and serum has been associated,vith accelerated j oint damage in patients with rheumatoid arthritis (RA) and osteoarthri tis. To fully understand the reasons for fluctuations of COMP levels, we studied the biosynthesis of this molecule in cells derived from joi nt tissues. Methods. Synovial cells were derived from synovial tissues of patients with RA, and human articular chondrocytes were prepared f rom normal articular cartilage, Analysis by Northern blotting was used to evaluate steady-state levels of COMP messenger RNA (mRNA), while s ecretion of the protein into culture media was analyzed by Western blo tting. Expression of COMP in synovial tissues nas studied by reverse t ranscriptase-polymerase chain reaction analysis and by in situ hybridi zation, Results, COMP was synthesized and secreted by synovial cells a s well as by articular chondrocytes in culture, The basal rate of synt hesis was very low; however, COMP biosynthesis in both cell population s was induced very strongly by transforming growth factor beta 1 (TGF beta 1), Interleukin-1 beta counteracted COMP induction by TGF-beta 1, COMP was not detected in culture media of skin or fetal lung fibrobla sts, either in the absence or the presence of TGF beta 1, COMP mRNA wa s also present in fresh synovial tissue specimens obtained from patien ts with RA. Conclusion. COMP is synthesized and secreted not only by a rticular chondrocytes, but also by synovial fibroblasts. The demonstra tion of COMP expression in surgical specimens of synovial tissues sugg ests that the inflamed synovium may provide an additional source for t he elevated levels of COMP observed in arthritis. Thus, increased COMP levels in body fluids may be indicative of active synovitis as well a s of accelerated joint erosion.