Prostaglandins in human cartilage metabolism.

(1) Human cartilage, both non-arthritic (N) and arthritic, is extremely sensitive to inhibition of glycosaminoglycan (GAG) synthesis by low concentrations of interleukin 1 (IL1). Local episodic synthesis and secretion of sub-nanogram concentrates of the cytokine is considered to play a significant role in the pathogenesis of osteoarthritis (OA) by preventing matrix repair. (2) The synthesis of IL1 can be controlled by prostaglandins (PGs), which may explain why the inhibitory action can be at least partially overcome by the action of the PG analogue Misoprostol in the dose range 10-100 ng/ml. It is suggested that this action is due to the suppression of a positive feedback loop for local IL1 synthesis and secretion. (3) Certain non-steroidal anti-inflammatory drugs (NSAIDs), in particular Indomethacin, Ibuprofen and Naproxen, cause inhibition of GAG synthesis, and hence may diminish the potentiality for repair in arthritic cartilage. It is suggested that these NSAIDs induce IL1 synthesis by diminishing PG levels. Misoprostol is able to reverse this effect at least partially. (4) Some cartilages in the presence of other NSAIDs, such as Diclofenac, which do not greatly inhibit chondrocyte matrix metabolism, nevertheless respond to the presence of Misoprostol by increased GAG synthetic activity. (5) The low mean matrix synthetic activity of human OA cartilages was significantly increased by Misoprostol. (6) Taken together, these studies substantiate the suggestion that Misoprostol is able to increase the repair potentiality of human OA cartilage, particularly during treatment with NSAIDs.