EFFECTS OF MISOPROSTOL AND PROSTAGLANDIN-E2 ON PROTEOGLYCAN BIOSYNTHESIS AND LOSS IN UNLOADED AND LOADED ARTICULAR-CARTILAGE EXPLANTS

The effects of misoprostol, a prostaglandin E1 analog, and prostagland in E2 on proteoglycan biosynthesis and loss were studied in unloaded a nd mechanically loaded mature bovine articular cartilage explants. The prostaglandins were administered daily at dosages of 0, 10, 100 and 1 000 eta g/ml for up to seven days, and proteoglycan biosynthesis deter mined by measurement of radiolabelled sulfate incorporation. The prese nce of misoprostol lead to a significant (p < 0.001) dose-dependent in hibition (30%-50%) in proteoglycan biosynthesis which was also depende nt on exposure time (p<0.05). A significant decrease in biosynthesis ( 34%) was also found for prostaglandin E2, but only at the highest dose (1000 eta g/ml). Proteoglycan catabolism rates were not affected by e ither substance as assessed by loss of newly synthesized proteoglycan. The application of a continuous cyclic mechanical compressive load (s tress of 1.0 MPa at 1 hertz for 24 hours) resulted in a significant in hibition of proteoglycan biosynthesis (up to 50%) as compared to unloa ded explants. However, there was no additive effect when mechanical lo ad and misoprostol or prostaglandin E2 were combined. These results su ggest that prostaglandins may have a role in the degenerative and repa ir process in various forms of arthritis where elevated intra-articula r levels of prostaglandin E2 are present.