Misoprostol, a prostaglandin E1 analogue, inhibits basic calcium phosphate crystal-induced mitogenesis and collagenase accumulation in human fibroblasts.
Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathy. BCP crystals induce the secretion of matrix-degrading enzymes such as collagenase. No prophylactic or therapeutic agents are recognized to ameliorate the cartilage damage associated with BCP deposits in joints. As a chondroprotective effect of prostaglandins (PG) has been suggested, we studied the effect of misoprostol, a PGE1 analogue, on BCP crystal-induced mitogenesis and collagenase messenger RNA (mRNA) accumulation in human fibroblasts (HF). Mitogenesis was determined by 3H-thymidine incorporation assays and collagenase mRNA accumulation by Northern blot analysis, in HF stimulated with BCP crystals in the presence or absence of misoprostol. Misoprostol caused concentration-dependent inhibition of BCP crystal-induced mitogenesis. The inhibition of BCP-stimulated mitogenesis was not specific as misoprostol also inhibited the mitogenic response to 10% serum. There was only 50 (+/-5)% inhibition of serum-induced mitogenesis by misoprostol at 500 ng/ml, the concentration that completely inhibited BCP crystal-induced mitogenesis. Misoprostol also inhibited the accumulation of collagenase mRNA in BCP-stimulated HF by 63%. These data suggest that misoprostol may inhibit the synovial proliferation and cartilage degradation that accompany BCP crystal deposition.
McCarthy
G M
GM
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Mitchell
P G
PG
Cheung
H S
HS
D015152:Blotting, Northern; D002130:Calcium Phosphates / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D017364:Collagenases / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D016595:Misoprostol / Q000494:pharmacology*; D008934:Mitogens / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000187:drug effects; D013582:Synovial Fluid / Q000378:metabolism
D002130:Calcium Phosphates; D008934:Mitogens; D012333:RNA, Messenger; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D016595:Misoprostol; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D017364:Collagenases; C485829:calcium phosphate, dibasic, anhydrous