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Research Article Free access | 10.1172/JCI119316

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

R C Billinghurst, L Dahlberg, M Ionescu, A Reiner, R Bourne, C Rorabeck, P Mitchell, J Hambor, O Diekmann, H Tschesche, J Chen, H Van Wart, and A R Poole

Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Department of Surgery, McGill University, Montreal, Quebec, Canada. cbillinghurst@shriners.mcgill.ca

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Published April 1, 1997 - More info

Published in Volume 99, Issue 7 on April 1, 1997
J Clin Invest. 1997;99(7):1534–1545. https://doi.org/10.1172/JCI119316.
© 1997 The American Society for Clinical Investigation
Published April 1, 1997 - Version history
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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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