Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.

  • R Clark Billinghurst, L Dahlberg, +10 authors A R Poole
  • Published 1997 in The Journal of clinical investigation

Abstract

We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes generated by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated 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 denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.

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@article{Billinghurst1997EnhancedCO, title={Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.}, author={R Clark Billinghurst and L Dahlberg and M Ionescu and A Reiner and R Bourne and Cecil H Rorabeck and P Mitchell and John E. Hambor and O Diekmann and H Tschesche and J Chen and Harold E Van Wart and A R Poole}, journal={The Journal of clinical investigation}, year={1997}, volume={99 7}, pages={1534-45} }