ENHANCED CLEAVAGE OF TYPE-II COLLAGEN BY COLLAGENASES IN OSTEOARTHRITIC ARTICULAR-CARTILAGE

We demonstrate the direct involvement of increased collagenase activit y in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carb oxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepi topes general ed by cleavage of native human type II collagen by colla genase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collag enase-2), and MMP-13 (collagenase-3). A secondary cleavage followed th e initial cleavage produced by these recombinant collagenases. This ge nerated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C( short) neoepitope in osteoarthritis (OA) compared to adult nonarthriti c cartilages as determined by immunoassay of cartilage extracts. A syn thetic preferential inhibitor of MMP-13 significantly reduced the unst imulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase (s) produced by chondrocytes is (are) involved in the cleavage and den aturation of type II collagen in articular cartilage, that this is inc reased in OA, and that MMP-13 may play a significant role in this proc ess.