TYPE II COLLAGEN CLEAVAGE BY MMP-13 INDUCED BY COOH-TERMINAL HEPARIN-BINDING FIBRONECTIN FRAGMENT IN BOVINE ARTICULAR CARTILAGE

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The study was aimed to examine the effects of a COOH-terminal heparin-binding fibronectin fragment (HBFN-f) on chondorcyte-mediated type II collagen cleavage by collagenase and proteoglycan degradation in bovine articular cartilage in explant culture. In contrast to intact fibronectin, HBFN-f was shown to stimulate type II collagen cleavage by collagenase in a dose-dependent manner following proteoglycan degradation, similar to cartilage breakdown induced by IL-1. Treatment with HBFN-f also resulted in elevated denaturation of type II collagen. Immunoblotting demonstrated that HBFN-f enhanced proMMP- 13 production as well as that of proMMP-3. An MMP- 13 preferential inhibitor or IL-1 receptor antagonist suppressed HBFN-f-induced collagen cleavage to control level. Our data demonstrate that HBFN-f can induce curly proteoglycan degradation and subsequent type II collagen cleavage. The latter is probably mediated by early proMMP- 13 induction involving an IL- 1 -dependent pathway. Our results, together with existing data on other fibronectin fragments, reveal that increased levels of these fragments, found in osteoarthritis and rheumatoid arthritis, may stimulate cartilage breakdown by mechanisms of the kind demonstrated in the present study.