TY - JOUR
T1 - Nitric-Oxide Mediates Suppression of Cartilage Proteoglycan Synthesis by Interleukin-1
AU - Taskiran, Dilek
AU - Stefanovicracic, Maja
AU - Georgescu, Helga
AU - Evans, Christoper
PY - 1994/4/15
Y1 - 1994/4/15
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1994.1426
DO - 10.1006/bbrc.1994.1426
M3 - Article
C2 - 7513156
AN - SCOPUS:0028238196
SN - 0006-291X
VL - 200
SP - 142
EP - 148
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -