Dexamethasone inhibits collagen degradation induced by the combination of interleukin-1 and plasminogen in cartilage explant culture

Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix metalloproteinases (MMP). However, in in vitr o 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 cu lture. Dexamethasone clearly blocked collagen degradation induced by the co mbination of interleukin-1 (IL-1) and plasminogen at the concentration of 1 0(-9) M, which 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 conversio n of plasminogen to plasmin, however, was not blocked by treatment with dex amethasone. These results suggest that the inhibitory effect of dexamethaso ne on collagen degradation may be due to suppression of MMP production rath er than suppression of fibrinolytic cascade. Thus, the ability of glucocort icoids to inhibit matrix degradation in vitro, which could be clearly shown by monitoring collagen degradation, may endorse their efficacy in animal O A models and suggest potential therapeutic effectiveness.