Collagen Degradation Induced by the Combination of IL-1.ALPHA. and Plasminogen in Rabbit Articular Cartilage Explant Culture.

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To investigate the effect of plasminogen on cartilage catabolism, we assessed collagen degradation in rabbit articular cartilage explants treated with or without plasminogen and interleukin-1α (IL-1α). The combination of IL-1α and plasminogen induced rapid collagen degradation, amounting to more than 60% of the total collagen by day 7, while neither IL-1α nor plasminogen alone had any effect. To examine the mechanism of collagen degradation induced by IL-1α and plasminogen, the matrix metalloproteinases (MMPs) in the culture supernatants were examined by ELISA, Western blotting and gelatin zymography. We found that the treatment with IL-1α induced MMP-1, MMP-3, and MMP-9. In addition, plasminogen converted the pro form of MMPs into the active form. Both a tissue inhibitor of metalloproteinases-1 (TIMP-1) and a synthetic hydroxamate MMP inhibitor prevented this collagen release. These results suggest that plasminogen causes collagen degradation via activation of MMPs induced by IL-1α.
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