Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1.
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.
Taskiran
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D
Ferguson Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, PA 15261.
Stefanovic-Racic
M
M
Georgescu
H
H
Evans
C
C
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D026423:S-Nitroso-N-Acetylpenicillamine; D013237:Stereoisomerism; D013431:Sulfates / Q000378:metabolism; D019323:omega-N-Methylarginine
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011506:Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D013431:Sulfates; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010396:Penicillamine