GLUCOCORTICOSTEROIDS INHIBIT DEGRADATION IN BOVINE CARTILAGE EXPLANTSSTIMULATED WITH CONCOMITANT PLASMINOGEN AND INTERLEUKIN-1-ALPHA

Objective: Glucocorticosteroids are beneficial in the treatment of ost eoarthritis (OA) in humans, and have been shown to protect cartilage i n animal models of OA. Therefore, we undertook the present study to in vestigate the in vitro effect of several glucocorticosteroids on carti lage degradation. Methods: Bovine articular cartilage explants labeled with [S-35] Sulfate and stimulated either with IL-1 alpha alone or wi th concomitant plasminogen plus IL-1 alpha were used in this study as an in vitro model of cartilage degradation. Clobetasol propionate, flu ocinolone-acetonide-21-acetate, prednisolone, triamcinolone and triamc inolone hexacetonide were the glucocorticosteroids investigated in a s eries of experiments, at concentrations ranging from 10 picomolar to 1 0 micromolar. Degradation in [S-35] Sulfate-labeled bovine articular c artilage explants was induced with IL-1 alpha or with concomitant IL-1 alpha plus human plasminogen. The effects of several glucocorticoster oids were studied, and a comparison between efficacy in explants stimu lated with IL-1 alpha alone or IL-1 alpha plus concomitant plasminogen was made. Glucocorticosteroid efficacy was expressed as percent inhib ition of degradation, and their IC(50)s were also calculated. Results: Glucocorticosteroids showed no protective effects on cartilage degrad ation in the presence of IL-1 alpha alone. When degradation was induce d by IL-1 alpha in the presence of concomitant human plasminogen, all the glucocorticosteroids showed statistically significant inhibition ( p < 0.05) with calculated IC(50)s of 450-2500 picomolar. Conclusion: T he inhibition of cartilage degradation by glucocorticosteroids may be due to down-regulation of urokinase plasminogen activator (u-PA) activ ity. It has been shown that u-PA may be the first enzyme in the cascad e of activation of pro-matrix metalloproteinases by the fibrinolytic s ystem. Inhibition of u-PA activity may be one explanation for the effi cacy of glucocorticosteroids observed in animal models of OA and with intraarticular injection in patients with OA.