Glucocorticosteroids inhibit degradation in bovine cartilage explants stimulated with concomitant plasminogen and interleukin-1 alpha.

Abstract

Glucocorticosteroids are beneficial in the treatment of osteoarthritis (OA) in humans, and have been shown to protect cartilage in animal models of OA. Therefore, we undertook the present study to investigate the in vitro effect of several glucocorticosteroids on cartilage degradation. Bovine articular cartilage explants labeled with [35S] Sulfate and stimulated either with IL-1 alpha alone or with concomitant plasminogen plus IL-1 alpha were used in this study as an in vitro model of cartilage degradation. Clobetasol propionate, fluocinolone-acetonide-21-acetate, prednisolone, triamcinolone and triamcinolone hexacetonide were the glucocorticosteroids investigated in a series of experiments, at concentrations ranging from 10 picomolar to 10 micromolar. Degradation in [35S] Sulfate-labeled bovine articular cartilage explants was induced with IL-1 alpha or with concomitant IL-1 alpha plus human plasminogen. The effects of several glucocorticosteroids were studied, and a comparison between efficacy in explants stimulated with IL-1 alpha alone or IL-1 alpha plus concomitant plasminogen was made. Glucocorticosteroid efficacy was expressed as percent inhibition of degradation, and their IC50S were also calculated. Glucocorticosteroids showed no protective effects on cartilage degradation in the presence of IL-1 alpha alone. When degradation was induced by IL-1 alpha in the presence of concomitant human plasminogen, all the glucocorticosteroids showed statistically significant.inhibition (p < 0.05) with calculated IC50S of 450-2500 picomolar. The inhibition of cartilage degradation by glucocorticosteroids may be due to down-regulation of urokinase plasminogen activator (u-PA) activity. It has been shown that u-PA may be the first enzyme in the cascade of activation of pro-matrix metalloproteinases by the fibrinolytic system. Inhibition of u-PA activity may be one explanation for the efficacy of glucocorticosteroids observed in animal models of OA and with intraarticular injection in patients with OA.