Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes.
OBJECTIVE
Cartilage oligomeric matrix protein (COMP) is a component of the extracellular matrix of articular cartilage. Its increased presence in synovial fluid and serum has been associated with accelerated joint damage in patients with rheumatoid arthritis (RA) and osteoarthritis. To fully understand the reasons for fluctuations of COMP levels, we studied the biosynthesis of this molecule in cells derived from joint tissues.


METHODS
Synovial cells were derived from synovial tissues of patients with RA, and human articular chondrocytes were prepared from normal articular cartilage. Analysis by Northern blotting was used to evaluate steady-state levels of COMP messenger RNA (mRNA), while secretion of the protein into culture media was analyzed by Western blotting. Expression of COMP in synovial tissues was studied by reverse transcriptase-polymerase chain reaction analysis and by in situ hybridization.


RESULTS
COMP was synthesized and secreted by synovial cells as well as by articular chondrocytes in culture. The basal rate of synthesis was very low; however, COMP biosynthesis in both cell populations was induced very strongly by transforming growth factor beta1 (TGFbeta1). Interleukin-1beta counteracted COMP induction by TGF-beta1. COMP was not detected in culture media of skin or fetal lung fibroblasts, either in the absence or the presence of TGFbeta1. COMP mRNA was also present in fresh synovial tissue specimens obtained from patients with RA.


CONCLUSIONS
COMP is synthesized and secreted not only by articular chondrocytes, but also by synovial fibroblasts. The demonstration of COMP expression in surgical specimens of synovial tissues suggests that the inflamed synovium may provide an additional source for the elevated levels of COMP observed in arthritis. Thus, increased COMP levels in body fluids may be indicative of active synovitis as well as of accelerated joint erosion.
Recklies
A D
AD
Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.
Baillargeon
L
L
White
C
C
D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D064235:Matrilin Proteins; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007375:Interleukin-1; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D016212:Transforming Growth Factor beta