NITRIC-OXIDE MEDIATES SUPPRESSION OF CARTILAGE PROTEOGLYCAN SYNTHESIS BY INTERLEUKIN-1


TASKIRAN D. , STEFANOVİCRACİC M., GEORGESCU H., EVANS C.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol.200, no.1, pp.142-148, 1994 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 200 Issue: 1
  • Publication Date: 1994
  • Doi Number: 10.1006/bbrc.1994.1426
  • Title of Journal : BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Page Numbers: pp.142-148

Abstract

Slices of rabbit articular cartilage synthesized large quantities of nitric oxide (NO) following exposure to human recombinant interleukin-1 beta (hrIL-1 beta) or rabbit synovial cytokines (CAF). Each of these stimuli also strongly suppressed the biosynthetic incorporation of (SO42-)-S-35 into the glycosaminoglycans (GAGs) of cartilage proteoglycans. Treatment of cartilage fragments with L-N-G-monomethylarginine (L-NMA), a competitive inhibitor of NO synthase, both inhibited NO synthesis in response to IL-1 and CAF and restored proteoglycan synthesis. D-NMA was inactive in this regard, and L-arginine reversed the effects of L-NMA. S-nitrosylacetylpenicillamine (SNAP), an organic donor of NO, reversibly mimicked the effect of IL-1 and CAF on (SO42-)-S-35 incorporation. These data suggest that endogenously synthesized NO is the mediator which reduces cartilage proteoglycan synthesis in response to cytokines such as IL-1 and CAF. Antagonists of NO production may promote cartilage matrix synthesis and thus have potential as chondroprotective or chondroreparative agents. (C) 1994 Academic Press, Inc.