Dexamethasone Inhibits Collagen Degradation Induced by the Combination of Interleukin-1 and Plasminogen in Cartilage Explant Culture

概要

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Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix matalloproteinases (MMP). However, in in vitro studies, their inhibitory effects on matrix degradation of cartilage have not been well documented by monitoring aggrecan. Collagen was monitored in this study to examine the effects of dexamethasone in cartilage explant culture. Dexamethasone cleary blocked collagen degradation induced by the combination of interleukin-1 (IL-1) and plasminogen at the concentration of 10^<-9>M, whcih is much lower than the concentrations reportedly required to inhibit matrix synthesis. In addition, MMP-1 and MMP-3 were suppressed by dexamethasone treatment in a similar range of concentrations. The conversion of plasminogen to plasmin, however, was not blocked by treatment with dexamethasone. These results suggest that the inhibitory effect of dexamethasone on collagen degradation may be due to suppression of MMP production rather than suppression of fibrinolytic cascade. Thus, the ability of glucocorticoids to inhibit matrix degradation in vitro, which could be clearly shown by monitoring collagen degradation, may endorse their efficacy in animal OA models and suggest potential therapeutic effectiveness.
公益社団法人日本薬学会の論文
1999-07-15