TISSUE INHIBITOR OF METALLOPROTEINASE-2 (TIMP-2) MESSENGER-RNA IS CONSTITUTIVELY EXPRESSED IN BOVINE, HUMAN NORMAL, AND OSTEOARTHRITIC ARTICULAR CHONDROCYTES

Tissue inhibitors of metalloproteinases (TIMPs) inhibit the extracellu lar matrix (ECM) metalloproteinases (MMPs). To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ab ility of chondrocytes to express TIMP-2 and its regulation by agents f ound in inflammed joints was investigated. The constitutive TIMP-2 mRN A expression was demonstrated in chondrocytes from normal bovine, huma n OA and normal cartilage. The cross-hybridization of human and bovine TIMP-2 suggested its evolutionary conservation. Serum, IL-1, IL-6 and TGF-beta were unable to augment considerably the basal expression of TIMP-2 mRNA. TIMP-1 RNA expression in chondrocytes from human OA carti lage was elevated compared to non-OA chondrocytes, while TIMP-2 mRNA l evels were similar in both. IL-1 beta, IL-6 and TGF-beta did not affec t TIMP-2 expression but TGF-beta induced TIMP-1 mRNA in human OA chond rocytes. TIMP-2 and TIMP-1 are therefore differentially regulated in c hondrocytes and the basal TIMP-2 levels may be needed for the cartilag e ECM integrity. (C) 1996 Wiley-Liss, Inc.