title: Fibronectin-mediated adhesion rescues cell cycle arrest induced by fibroblast growth factor-1 by decreased expression of p21(cip/waf) in human chondrocytes.
abstract: In chondrocytes, fibroblast growth factors (FGFs) inhibit chondrocytes proliferation by upregulation of the cell cycle inhibitor p21(cip/waf). In this report, we first investigated the roles of fibronectin (FN)-mediated cell adhesion in the modulation of FGF-1's antiproliferative function in chondrocytes. In this study, we found that FN-mediated signaling could rescue cell cycle arrest induced by FGF-1 in primary human chondrocytes. This prevention of cell cycle arrest induced by FGF-1 was due to the suppression of the cell cycle inhibitor p21(cip/waf) expression on adhesion to FN and its downstream activation of signaling pathways. Finally, we showed that this rescue induced by FN-mediated adhesion is dependent on the extracellular regulated kinase (ERK) signaling pathway. Taken together, these studies support that, despite FGF-FGF receptor's growth-inhibitory function, the FN-mediated signaling can collaborate to compensate for its negative effect on chondrocytes proliferation, providing evidence for cross talk between signals emerging from these cell surface molecules in chondrocyte.
authors.affiliation: Department of Biochemistry, Inha University College of Medicine, Jung-Gu, Incheon 400-712, Korea. juhjang@inha.ac.kr
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005353:Fibronectins; D016220:Fibroblast Growth Factor 1