FGF18 accelerates osteoblast differentiation by upregulating <i><scp>B</scp>mp2</i> expression

  • Tomoko Nagayama
    Section of Molecular Craniofacial Embryology Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan
  • Shigeru Okuhara
    Section of Molecular Craniofacial Embryology Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan
  • Masato S. Ota
    Section of Molecular Craniofacial Embryology Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan
  • Noriko Tachikawa
    Section of Oral Implantology and Regenerative Dental Medicine Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan
  • Shohei Kasugai
    Section of Oral Implantology and Regenerative Dental Medicine Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan
  • Sachiko Iseki
    Section of Molecular Craniofacial Embryology Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences Tokyo Japan

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<jats:title>Abstract</jats:title><jats:p>Fibroblast growth factor (<jats:styled-content style="fixed-case">FGF</jats:styled-content>) signaling is involved in skeletal development. Among total 22 <jats:styled-content style="fixed-case">FGFs</jats:styled-content>, it is suggested that <jats:styled-content style="fixed-case">FGF18</jats:styled-content> functions in promotion of osteoblast differentiation. In order to elucidate the mechanism of <jats:styled-content style="fixed-case">FGF18</jats:styled-content>‐dependent acceleration of osteogenesis, we implanted <jats:styled-content style="fixed-case">rhFGF18</jats:styled-content> soaked beads over mouse fetal coronal sutures using <jats:italic>ex‐utero</jats:italic> surgery. The coronal suture area comprises the peripheries of the developing frontal and parietal bones, separated by the sutural mesenchyme. <jats:styled-content style="fixed-case">rhFGF18</jats:styled-content> accelerated osteogenesis by promoting connection of the frontal and parietal bone domains, resulting in elimination of the sutural mesenchyme. Expression of <jats:italic><jats:styled-content style="fixed-case">F</jats:styled-content>gf receptors</jats:italic>, <jats:italic><jats:styled-content style="fixed-case">F</jats:styled-content>gfr1</jats:italic>, ‐<jats:italic>2</jats:italic> and ‐<jats:italic>3</jats:italic> involved in skeletal development, was maintained or upregulated in the developing bone domains, consistent with enhanced osteogenesis. <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>one morphogenetic protein</jats:italic> (<jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>mp</jats:italic>) <jats:italic>2</jats:italic> was specifically upregulated in the skeletogenic layer and the application of <jats:styled-content style="fixed-case">B</jats:styled-content>mp antagonist, rmNoggin, inhibited <jats:styled-content style="fixed-case">rhFGF18</jats:styled-content>‐dependent upregulation of osteoblast markers. These results suggest that <jats:styled-content style="fixed-case">FGF18</jats:styled-content> accelerates osteogenesis by upregulation of <jats:italic><jats:styled-content style="fixed-case">B</jats:styled-content>mp2</jats:italic> as well as maintenance or upregulation of <jats:italic><jats:styled-content style="fixed-case">F</jats:styled-content>gfr1</jats:italic>, ‐<jats:italic>2</jats:italic> and ‐<jats:italic>3</jats:italic> expression in osteoblasts.</jats:p>

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