MISOPROSTOL, A PROSTAGLANDIN-E1 ANALOG, INHIBITS BASIC CALCIUM-PHOSPHATE CRYSTAL-INDUCED MITOGENESIS AND COLLAGENASE ACCUMULATION IN HUMAN FIBROBLASTS

Synovial fluid basic calcium Phosphate (BCP) crystals are associated w ith severe destructive arthropathy. BCP crystals induce the secretion of matrix-degrading enzymes such as collagenase. No prophylactic or th erapeutic agents are recognized to ameliorate the cartilage damage ass ociated with BCP deposits in joints. As a chondroprotective effect of prostaglandins (PG) has been suggested, we studied the effect of misop rostol, a PGE1 analogue, on BCP crystal-induced mitogenesis and collag enase messenger RNA (mRNA) accumulation in human fibroblasts (HF). Mit ogenesis was determined by H-3-thymidine incorporation assays and coll agenase mRNA accumulation by Northern blot analysis, in HF stimulated with BCP crystals in the presence or absence of misoprostol. Misoprost ol caused concentration-dependent inhibition of BCP crystal-induced mi togenesis. The inhibition of BCP-stimulated mitogenesis was not specif ic as misoprostol also inhibited the mitogenic response to 10% serum. There was only 50 (+/-5)% inhibition of serum-induced mitogenesis by m isoprostol at 500 ng/ml, the concentration that completely inhibited B CP crystal-induced mitogenesis. Misoprostol also inhibited the accumul ation of collagenase mRNA in BCP-stimulated HF by 63%. These data sugg est that misoprostol may inhibit the synovial proliferation and cartil age degradation that accompany BCP crystal deposition.