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Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo

OBJECTIVE: The articular cartilage is known to be highly mechanosensitive, and a number of mechanosensing mechanisms have been proposed as mediators of the cellular responses to altered mechanical load. These pathways are likely to be important in tissue homeostasis as well as in the pathogenesis of...

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Autores principales: Chong, Ka-Wing, Chanalaris, Anastasios, Burleigh, Annika, Jin, Huilin, Watt, Fiona E, Saklatvala, Jeremy, Vincent, Tonia L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley Periodicals, Inc 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992838/
https://www.ncbi.nlm.nih.gov/pubmed/23740825
http://dx.doi.org/10.1002/art.38039
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author Chong, Ka-Wing
Chanalaris, Anastasios
Burleigh, Annika
Jin, Huilin
Watt, Fiona E
Saklatvala, Jeremy
Vincent, Tonia L
author_facet Chong, Ka-Wing
Chanalaris, Anastasios
Burleigh, Annika
Jin, Huilin
Watt, Fiona E
Saklatvala, Jeremy
Vincent, Tonia L
author_sort Chong, Ka-Wing
collection PubMed
description OBJECTIVE: The articular cartilage is known to be highly mechanosensitive, and a number of mechanosensing mechanisms have been proposed as mediators of the cellular responses to altered mechanical load. These pathways are likely to be important in tissue homeostasis as well as in the pathogenesis of osteoarthritis. One important injury-activated pathway involves the release of pericellular fibroblast growth factor 2 (FGF-2) from the articular cartilage. Using a novel model of murine cartilage injury and surgically destabilized joints in mice, we examined the extent to which FGF-2 contributes to the cellular gene response to injury. METHODS: Femoral epiphyses from 5-week-old wild-type mice were avulsed and cultured in serum-free medium. Explant lysates were Western blotted for phospho-JNK, phospho-p38, and phospho-ERK or were fixed for immunohistochemical analysis of the nuclear translocation of p65 (indicative of NF-κB activation). RNA was extracted from injured explants, rested explants that had been stimulated with recombinant FGF-2 or FGF-18, or whole joints from either wild-type mice or FGF-2(−/−) mice. Reverse transcription–polymerase chain reaction was performed to examine a number of inflammatory response genes that had previously been identified in a microarray analysis. RESULTS: Murine cartilage avulsion injury resulted in rapid activation of the 3 MAP kinase pathways as well as NF-κB. Almost all genes identified in murine joints following surgical destabilization were also regulated in cartilage explants upon injury. Many of these genes, including those for activin A (Inhba), tumor necrosis factor–stimulated gene 6 (Tnfaip6), matrix metalloproteinase 19 (Mmp19), tissue inhibitor of metalloproteinases 1 (Timp1), and podoplanin (Pdpn), were significantly FGF-2 dependent following injury to cartilage in vitro and to joint tissues in vivo. CONCLUSION: FGF-2–dependent gene expression occurs in vitro and in vivo in response to cartilage/joint injury in mice.
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spelling pubmed-39928382014-04-22 Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo Chong, Ka-Wing Chanalaris, Anastasios Burleigh, Annika Jin, Huilin Watt, Fiona E Saklatvala, Jeremy Vincent, Tonia L Arthritis Rheum Chondrocyte Biology OBJECTIVE: The articular cartilage is known to be highly mechanosensitive, and a number of mechanosensing mechanisms have been proposed as mediators of the cellular responses to altered mechanical load. These pathways are likely to be important in tissue homeostasis as well as in the pathogenesis of osteoarthritis. One important injury-activated pathway involves the release of pericellular fibroblast growth factor 2 (FGF-2) from the articular cartilage. Using a novel model of murine cartilage injury and surgically destabilized joints in mice, we examined the extent to which FGF-2 contributes to the cellular gene response to injury. METHODS: Femoral epiphyses from 5-week-old wild-type mice were avulsed and cultured in serum-free medium. Explant lysates were Western blotted for phospho-JNK, phospho-p38, and phospho-ERK or were fixed for immunohistochemical analysis of the nuclear translocation of p65 (indicative of NF-κB activation). RNA was extracted from injured explants, rested explants that had been stimulated with recombinant FGF-2 or FGF-18, or whole joints from either wild-type mice or FGF-2(−/−) mice. Reverse transcription–polymerase chain reaction was performed to examine a number of inflammatory response genes that had previously been identified in a microarray analysis. RESULTS: Murine cartilage avulsion injury resulted in rapid activation of the 3 MAP kinase pathways as well as NF-κB. Almost all genes identified in murine joints following surgical destabilization were also regulated in cartilage explants upon injury. Many of these genes, including those for activin A (Inhba), tumor necrosis factor–stimulated gene 6 (Tnfaip6), matrix metalloproteinase 19 (Mmp19), tissue inhibitor of metalloproteinases 1 (Timp1), and podoplanin (Pdpn), were significantly FGF-2 dependent following injury to cartilage in vitro and to joint tissues in vivo. CONCLUSION: FGF-2–dependent gene expression occurs in vitro and in vivo in response to cartilage/joint injury in mice. Wiley Periodicals, Inc 2013-09 2013-08-26 /pmc/articles/PMC3992838/ /pubmed/23740825 http://dx.doi.org/10.1002/art.38039 Text en © 2013 The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chondrocyte Biology
Chong, Ka-Wing
Chanalaris, Anastasios
Burleigh, Annika
Jin, Huilin
Watt, Fiona E
Saklatvala, Jeremy
Vincent, Tonia L
Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title_full Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title_fullStr Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title_full_unstemmed Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title_short Fibroblast Growth Factor 2 Drives Changes in Gene Expression Following Injury to Murine Cartilage In Vitro and In Vivo
title_sort fibroblast growth factor 2 drives changes in gene expression following injury to murine cartilage in vitro and in vivo
topic Chondrocyte Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992838/
https://www.ncbi.nlm.nih.gov/pubmed/23740825
http://dx.doi.org/10.1002/art.38039
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