Nitric-Oxide Mediates Suppression of Cartilage Proteoglycan Synthesis by Interleukin-1

Dilek Taskiran, Maja Stefanovicracic, Helga Georgescu, Christoper Evans

Research output: Contribution to journalArticle

337 Scopus citations

Abstract

Slices of rabbit articular cartilage synthesized large quantities of nitric oxide (NO) following exposure to human recombinant interleukin-1β (hrIL-1β) or rabbit synovial cytokines (CAF). Each of these stimuli also strongly suppressed the biosynthetic incorporation of into the glycosaminoglycans (GAGs) of cartilage proteoglycans. Treatment of cartilage fragments with L-NG-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 35SO2-4 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.

Original languageEnglish (US)
Pages (from-to)142-148
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume200
Issue number1
DOIs
StatePublished - Apr 15 1994

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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