{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:43:54Z","timestamp":1790833434556,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,10,1]]},"abstract":"<jats:p> Chondrocytes in arthritic cartilage respond poorly to insulin-like growth factor I (IGF-I). Studies with inducible nitric oxide synthase (iNOS) knockout mice suggest that NO is responsible for part of the cartilage insensitivity to IGF-I. These studies characterize the relationship between NO and chondrocyte responses to IGF-I in vitro, and define a mechanism by which NO decreases IGF-I stimulation of chondrocyte proteoglycan synthesis. Lapine cartilage slices, chondrocytes, and cartilage from osteoarthritic (OA) human knees were exposed to NO from the donors S-nitroso- N-acetylpenicillamine (SNAP) or ( Z)-1-[2-(2-aminoethyl)- N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate] (DETA NONOate), by transduction with adenoviral transfer of iNOS (Ad-iNOS), or by activation with interleukin-1 (IL-1). NO synthesis was estimated from medium nitrite, and proteoglycan synthesis was measured as incorporation of <jats:sup>35<\/jats:sup>SO<jats:sub>4<\/jats:sub>. IGF-I receptor phosphorylation was evaluated with Western analysis. SNAP, DETA NONOate, endogenously synthesized NO in Ad-iNOS-transduced cells, or IL-1 activation decreased IGF-I-stimulated proteoglycan synthesis in cartilage and monolayer cultures of chondrocytes. OA cartilage responded poorly to IGF-I; however, the response to IGF-I was restored by culture with N <jats:sup>G<\/jats:sup>-monomethyl-l-arginine(l-NMA). IGF-I receptor phosphotyrosine was diminished in chondrocytes exposed to NO. These studies show that NO is responsible for part of arthritic cartilage\/chondrocyte insensitivity to anabolic actions of IGF-I; inhibition of receptor autophosphorylation is potentially responsible for this effect. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.279.4.c961","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T23:12:23Z","timestamp":1514157143000},"page":"C961-C969","source":"Crossref","is-referenced-by-count":95,"title":["Nitric oxide inhibits chondrocyte response to IGF-I: inhibition of IGF-IR\u03b2 tyrosine phosphorylation"],"prefix":"10.1152","volume":"279","author":[{"given":"R. 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