title: Fibroblast growth factor 2 drives changes in gene expression following injury to murine cartilage in vitro and in vivo.
abstract: 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.
  
  
  CONCLUSIONS
  FGF-2-dependent gene expression occurs in vitro and in vivo in response to cartilage/joint injury in mice.
authors.affiliation: Kennedy Institute of Rheumatology and University of Oxford, London, UK.
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Chong
authors.forename: Anastasios
authors.initials: A
authors.lastname: Chanalaris
authors.forename: Annika
authors.initials: A
authors.lastname: Burleigh
authors.forename: Huilin
authors.initials: H
authors.lastname: Jin
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Watt
authors.forename: Jeremy
authors.initials: J
authors.lastname: Saklatvala
authors.forename: Tonia L
authors.initials: TL
authors.lastname: Vincent
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases