Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1

Biochem Biophys Res Commun. 1994 Apr 15;200(1):142-8. doi: 10.1006/bbrc.1994.1426.


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 35SO4(2-) 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 35SO4(2-) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Cells, Cultured
  • Glycosaminoglycans / biosynthesis*
  • Humans
  • Interleukin-1 / pharmacology*
  • Kinetics
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Proteins / pharmacology
  • Proteoglycans / biosynthesis*
  • Rabbits
  • Recombinant Proteins / pharmacology*
  • S-Nitroso-N-Acetylpenicillamine
  • Stereoisomerism
  • Sulfates / metabolism
  • omega-N-Methylarginine


  • Glycosaminoglycans
  • Interleukin-1
  • Proteins
  • Proteoglycans
  • Recombinant Proteins
  • Sulfates
  • omega-N-Methylarginine
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Penicillamine