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Titolo:
OUTSIDE-IN SIGNALING IN THE CHONDROCYTE - NITRIC-OXIDE DISRUPTS FIBRONECTIN-INDUCED ASSEMBLY OF A SUBPLASMALEMMAL ACTIN RHO-A FOCAL ADHESION KINASE SIGNALING COMPLEX
Autore:
CLANCY RM; REDISKE J; TANG XY; NIJHER N; FRENKEL S; PHILIPS M; ABRAMSON SB;
Indirizzi:
HOSP JOINT DIS & MED CTR,DEPT RHEUMATOL,301 E 17TH ST NEW YORK NY 10003 NYU,MED CTR,DEPT MED,DIV RHEUMATOL NEW YORK NY 10003 NOVARTIS PHARMACEUT,RES DEPT,DIV PHARMACEUT SUMMIT NJ 07091
Titolo Testata:
The Journal of clinical investigation
fascicolo: 7, volume: 100, anno: 1997,
pagine: 1789 - 1796
SICI:
0021-9738(1997)100:7<1789:OSITC->2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT PROTEIN-KINASE; HUMAN ARTICULAR CHONDROCYTES; PROTEOGLYCAN SYNTHESIS; ADP-RIBOSYLATION; SYNOVIAL-FLUID; GROWTH-FACTORS; CELL-ADHESION; STRESS FIBERS; EXPRESSION; CARTILAGE;
Keywords:
CARTILAGE; EXTRACELLULAR MATRIX; INTEGRIN SIGNALING; FOCAL ADHESION COMPLEX; CYCLIC GMP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
R.M. Clancy et al., "OUTSIDE-IN SIGNALING IN THE CHONDROCYTE - NITRIC-OXIDE DISRUPTS FIBRONECTIN-INDUCED ASSEMBLY OF A SUBPLASMALEMMAL ACTIN RHO-A FOCAL ADHESION KINASE SIGNALING COMPLEX", The Journal of clinical investigation, 100(7), 1997, pp. 1789-1796

Abstract

Elevated levels of fibronectin (Fn) in articular cartilage have been linked to the progression of both rheumatoid and osteoarthritis. In this study, we examined intracellular events which follow ligation of Fnto its receptor, the integrin alpha 5 beta 1. In addition, we examined the regulatory influence of nitric oxide on these events, since thisfree radical has been implicated in cartilage degradation, Exposure of chondrocytes to Fn-coated beads resulted in the circumferential clustering of the alpha 5 beta 1 integrin receptor, which was accompanied by the subplasmalemmal assembly of a focal activation complex comprised of F-actin, the tyrosine kinase, focal adhesion kinase (FAK), the ras related G protein rho A, as well as tyrosine-phosphorylated proteins. Treatment with exogenous nitric oxide (NO) or catabolic cytokines which induce nitric oxide synthase blocked the assembly of F-actin, FAK,rho A and tyrosine-phosphorylated proteins while not affecting the total number of beads bound per cell nor the clustering of alpha 5 beta 1 integrin. Use of a cGMP antagonist (Rp-8-Br cGMPS) or cGMP agonist (Sp-cGMPS) either abolished or mimicked the NO effect, respectively, Adherence of chondrocytes to fibronectin enhanced proteoglycan synthesisby twofold (vs, albumin), In addition, basic fibroblast growth factor(FGF) and insulin growth factor (IGF-1) induced proteoglycan synthesis in chondrocytes adherent to Fn but not albumin suggesting a costimulatory signal transduced by alpha 5 beta 1 and the FGF receptor, Both constitutive and FGF stimulated proteoglycan synthesis were completely inhibited by nitric oxide, These data indicate that the ligation of alpha 5 beta 1 in the chondrocyte induced the intracellular assembly of an activation complex comprised of the cytoplasmic tail of alpha 5 beta 1 integrin, actin, and the signaling molecules rho A and FAK, We show that NO inhibits the assembly of the intracellular activation complex and the synthesis of proteoglycans, but has no effect on the extracellular aggregation of alpha 5 beta 1 integrin, These observations provide a basis by which nitric oxide can interfere with chondrocyte functions by affecting chondrocyte-matrix interactions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 08:49:46