title: FGF-2 acts through an ERK1/2 intracellular pathway to affect osteoblast differentiation.
abstract: An abundance of genetic and experimental data have suggested that fibroblast growth factor (FGF) signaling plays a central role in physiological and pathological cranial suture fusion. Although alterations in the differentiation and proliferation of sutural osteoblasts may be a key mediator of this process, the mechanisms by which FGF signaling regulates osteoblast differentiation remain incompletely understood. In the current study, the authors show that recombinant human FGF-2 alters osteoblastic expression of bone morphogenetic protein-2 and Msx-2 in vitro to favor cellular differentiation and osteoinduction. The ERK1/2 intracellular signaling cascade was shown to be necessary for recombinant human FGF-2-mediated bone morphogenetic protein-2 transcriptional changes. Furthermore, the cellular production of an intermediate transcriptional modifier was found to be necessary for the recombinant human FGF-2-mediated gene expression changes in bone morphogenetic protein-2 and Msx-2. Together, these findings offer new insight into the mechanisms by which FGF-2 modulates osteoblast biology.
authors.affiliation: Department of Surgery, Stanford University School of Medicine, Stanford, Calif 94305-5148, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Spector
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Mathy
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Warren
authors.forename: Randall P
authors.initials: RP
authors.lastname: Nacamuli
authors.forename: Hanjoon M
authors.initials: HM
authors.lastname: Song
authors.forename: Kelly
authors.initials: K
authors.lastname: Lenton
authors.forename: Kenton D
authors.initials: KD
authors.lastname: Fong
authors.forename: Dongyu T
authors.initials: DT
authors.lastname: Fang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000502:physiology*; D015151:Immunoblotting; D010006:Osteoblasts / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D012886:Skull / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases