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A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation

Activating mutations in FGF receptor 3 (FGFR3) cause several human dwarfism syndromes by affecting both chondrocyte proliferation and differentiation. Using microarray and biochemical analyses of FGF-treated rat chondrosarcoma chondrocytes, we show that FGF inhibits chondrocyte proliferation by init...

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Detalles Bibliográficos
Autores principales: Dailey, Lisa, Laplantine, Emmanuel, Priore, Riccardo, Basilico, Claudio
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172997/
https://www.ncbi.nlm.nih.gov/pubmed/12821644
http://dx.doi.org/10.1083/jcb.200302075
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author Dailey, Lisa
Laplantine, Emmanuel
Priore, Riccardo
Basilico, Claudio
author_facet Dailey, Lisa
Laplantine, Emmanuel
Priore, Riccardo
Basilico, Claudio
author_sort Dailey, Lisa
collection PubMed
description Activating mutations in FGF receptor 3 (FGFR3) cause several human dwarfism syndromes by affecting both chondrocyte proliferation and differentiation. Using microarray and biochemical analyses of FGF-treated rat chondrosarcoma chondrocytes, we show that FGF inhibits chondrocyte proliferation by initiating multiple pathways that result in the induction of antiproliferative functions and the down-regulation of growth-promoting molecules. The initiation of growth arrest is characterized by the rapid dephosphorylation of the retinoblastoma protein (pRb) p107 and repression of a subset of E2F target genes by a mechanism that is independent of cyclin E–Cdk inhibition. In contrast, hypophosphorylation of pRb and p130 occur after growth arrest is first detected, and may contribute to its maintenance. Importantly, we also find a number of gene expression changes indicating that FGF promotes many aspects of hypertrophic differentiation, a notion supported by in situ analysis of developing growth plates from mice expressing an activated form of FGFR3. Thus, FGF may coordinate the onset of differentiation with chondrocyte growth arrest in the developing growth plate.
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spelling pubmed-21729972008-05-01 A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation Dailey, Lisa Laplantine, Emmanuel Priore, Riccardo Basilico, Claudio J Cell Biol Article Activating mutations in FGF receptor 3 (FGFR3) cause several human dwarfism syndromes by affecting both chondrocyte proliferation and differentiation. Using microarray and biochemical analyses of FGF-treated rat chondrosarcoma chondrocytes, we show that FGF inhibits chondrocyte proliferation by initiating multiple pathways that result in the induction of antiproliferative functions and the down-regulation of growth-promoting molecules. The initiation of growth arrest is characterized by the rapid dephosphorylation of the retinoblastoma protein (pRb) p107 and repression of a subset of E2F target genes by a mechanism that is independent of cyclin E–Cdk inhibition. In contrast, hypophosphorylation of pRb and p130 occur after growth arrest is first detected, and may contribute to its maintenance. Importantly, we also find a number of gene expression changes indicating that FGF promotes many aspects of hypertrophic differentiation, a notion supported by in situ analysis of developing growth plates from mice expressing an activated form of FGFR3. Thus, FGF may coordinate the onset of differentiation with chondrocyte growth arrest in the developing growth plate. The Rockefeller University Press 2003-06-23 /pmc/articles/PMC2172997/ /pubmed/12821644 http://dx.doi.org/10.1083/jcb.200302075 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Dailey, Lisa
Laplantine, Emmanuel
Priore, Riccardo
Basilico, Claudio
A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title_full A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title_fullStr A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title_full_unstemmed A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title_short A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation
title_sort network of transcriptional and signaling events is activated by fgf to induce chondrocyte growth arrest and differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172997/
https://www.ncbi.nlm.nih.gov/pubmed/12821644
http://dx.doi.org/10.1083/jcb.200302075
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