title: FGF18 accelerates osteoblast differentiation by upregulating Bmp2 expression.
abstract: Fibroblast growth factor (FGF) signaling is involved in skeletal development. Among total 22 FGFs, it is suggested that FGF18 functions in promotion of osteoblast differentiation. In order to elucidate the mechanism of FGF18-dependent acceleration of osteogenesis, we implanted rhFGF18 soaked beads over mouse fetal coronal sutures using ex-utero surgery. The coronal suture area comprises the peripheries of the developing frontal and parietal bones, separated by the sutural mesenchyme. rhFGF18 accelerated osteogenesis by promoting connection of the frontal and parietal bone domains, resulting in elimination of the sutural mesenchyme. Expression of Fgf receptors, Fgfr1, -2 and -3 involved in skeletal development, was maintained or upregulated in the developing bone domains, consistent with enhanced osteogenesis. Bone morphogenetic protein (Bmp) 2 was specifically upregulated in the skeletogenic layer and the application of Bmp antagonist, rmNoggin, inhibited rhFGF18-dependent upregulation of osteoblast markers. These results suggest that FGF18 accelerates osteogenesis by upregulation of Bmp2 as well as maintenance or upregulation of Fgfr1, -2 and -3 expression in osteoblasts.
authors.affiliation: Section of Molecular Craniofacial Embryology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagayama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okuhara
authors.forename: Masato S
authors.initials: MS
authors.lastname: Ota
authors.forename: Noriko
authors.initials: N
authors.lastname: Tachikawa
authors.forename: Shohei
authors.initials: S
authors.lastname: Kasugai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Iseki
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis* / Q000378:metabolism; D002454:Cell Differentiation; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D017468:Receptors, Fibroblast Growth Factor; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors