PROSTAGLANDINS IN HUMAN CARTILAGE METABOLISM

(1) Human cartilage, both non-arthritic (N) and arthritic, is extremel y sensitive to inhibition of glycosaminoglycan (GAG) synthesis by low concentrations of interleukin 1 (IL1). Local episodic synthesis and se cretion 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 b y prostaglandins (PGs), which may explain why the inhibitory action ca n be at least partially overcome by the action of the PG analogue Miso prostol in the dose range 10-100 ng/ml. It is suggested that this anal ogue is due to the suppression of a positive feedback loop for local I L1 synthesis and secretion. (3) Certain non-steroidal anti-inflammator y drugs (NSAIDs), in particular Indomethacin, lbuprofen and Naproxen, cause inhibition of GAG synthesis, and hence may diminish the potentia lity for repair in arthritic cartilage. It is suggested that these NSA IDs 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 in hibit chondrocyte matrix metabolism, nevertheless respond to the prese nce of Misoprostol by increased GAG synthetic activity. (5) The low me an matrix synthetic activity of human OA cartilages was significantly increased by Misoprostol. (6) Taken together, these studies substantia te the suggestion that Misoprostol is able to increase the repair pote ntiality of human OA cartilage. particularly during treatment with NSA IDs.