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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

✍ Scribed by W.D. Shingleton; A.J. Ellis; A.D. Rowan; T.E. Cawston


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
237 KB
Volume
79
Category
Article
ISSN
0730-2312

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✦ Synopsis


Retinoic acid (RetA) and interleukin-1␣ (IL-1) 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-1 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-1 stimulates pro-collagenase secretion which, when activated, exceeds the local concentration of TIMP. Thus in the later stages of culture collagen destruction occurs. Both MMP-1 and MMP-13 were detected and appear to be involved in IL-1 ϩ 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.