Misoprostol, a prostaglandin E1 analogue, inhibits basic calcium phosphate crystal-induced mitogenesis and collagenase accumulation in human fibroblasts

Geraldine M. McCarthy, Peter G. Mitchell, Herman S. Cheung

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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 by3H-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.

Original languageEnglish (US)
Pages (from-to)434-437
Number of pages4
JournalCalcified Tissue International
Volume52
Issue number6
DOIs
StatePublished - Jun 1 1993
Externally publishedYes

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Keywords

  • Calcium crystals
  • Collagenase
  • Fibroblasts
  • Misoprostol
  • Mitogenesis

ASJC Scopus subject areas

  • Endocrinology

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