Effects of Misoprostol and Salicylate on Canine Osteoarthritis

The ability of misoprostol to reverse the deleterious changes induced in cartilage by sodium salicylate was tested using osteoarthritic canine and chondrocytes. Adult mongrel dogs were subjected to anterior cruciate ligament transection and dosed with either misoprostol, salicylate, or misoprostol plus salicylate. No significant differences were noted among the three groups in either gross and histological changes or general biochemical changes. This approach was abandoned since the levels of misoprostol attained by oral dosing were much lower than those required for domonstration of misoprostol effects in vitro. Next, chondrocytes were isolated from the osteoarthritic and contralateral knee joint cartilage of dogs 12 weeks after anterior cruciate ligament transection and cultured in alginate beads. The cultures were incubated with (3)H-proline and both the genetic types of collagen synthesized and the net synthesis of (3)H-hydroxyproline were determined. No drug or combination of drugs affected the genetic types of collagen synthesized. Total protein and collagen synthesis by chondrocytes was reduced in the presence of salicylate and increased in the presence of misoprostol. When osteoarthritic chondrocytes were incubated with both agents, the salicylate effect was reversed by misoprostol. Collagen synthesis by the chondrocytes from the contralateral knee was also suppressed by salicylate, but addition of misoprostol failed to restore synthesis. In summary, misoprostol, even at very high doses, has limited chondroprotective activity in canine cartilage, as judged from collagen synthetic activity.