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Retinoic acid combines with interleukin-1 to promote the degradation of collagen from bovine nasal cartilage: Matrix metalloproteinases-1 and-13 are involved in cartilage collagen breakdown

Lookup NU author(s): Dr William Shingleton, Emeritus Professor Drew Rowan, Emeritus Professor Tim Cawston


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Retinoic acid (RetA) and interleukin-1 alpha (IL-l) together can induce a reproducible release of proteoglycan fragments from bovine nasal cartilage in culture. However, release of collagen fragments with either agent alone is often variable. In this study over 70% of the total collagen was released from bovine nasal cartilage in culture by day 14 when RetA and IL-l were combined. This release was accompanied by the appearance of collagenolytic activity in the culture medium that cleaved collagen specifically at the 1/4/3/4 position. Tissue inhibitor of metalloproteinases (TIMP) activity was present at day 7 but low or absent in media from resorbing tissue at day 14. The breakdown of cartilage collagen could be prevented by the addition of BB-94, a specific metalloproteinase inhibitor. These results suggest that RetA promotes the early release of TIMP from the tissue and that IL-l stimulates pro-collagenase secretion which, when activated, exceeds the local concentration of TIMP. Th us in the later stages of culture collagen destruction occurs. Both MMP-1 and MMP-13 were detected and appear to be involved in IL-l + RetA induced bovine cartilage destruction. However, for the first time, we also present evidence to suggest that MMP-13 is the predominant collagenase in this system. I. Cell. Biochem. 79.519-531, 2000. (C) 2000 Wiley-Lisa Inc.

Publication metadata

Author(s): Shingleton WD, Ellis AJ, Rowan AD, Cawston TE

Publication type: Article

Publication status: Published

Journal: Journal of Cellular Biochemistry

Year: 2000

Volume: 79

Issue: 4

Pages: 519-531

ISSN (print): 0730-2312

ISSN (electronic): 1097-4644

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/1097-4644(20001215)79:4<519::AID-JCB10>3.0.CO;2-U


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