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Soluble FGFR2 with Apert mutation inhibits osteoblastic differentiation and proliferation

Background: Apert syndrome (AS) is characterized by craniosynostosis, midfacial hypoplasia and bony syndactyly.  Mutation of either S252W or P253R in Fibroblast Growth Factor Receptor (FGFR) 2 is known to be responsible for pathogenesis of AS.  These mutations in FGFR2 have been reported to act as a gain-of-functional mutation with a ligand-dependent manner due to a decrease of dissociation rate of FGFs from FGFR2 as well as a loss of ligand specificity of FGFR2. 

Objectives: To investigate the effects of soluble form of FGFR2 with or without Apert mutation (sFGFR2 or sFGFR2Ap) on MC3T3-E1 osteoblastic cells.

Methods: sFGFR2 and sFGFR2Ap were purified from the supernatant of COS-7 transfected with the sFGFR2IIIc-FLAG or sFGFR2Ap-FLAG expression vectors.  MC3T3-E1 cells which stably express FGFR2Ap-FLAG (MC3T3E1-Ap) were established.  The effects of sFGFR2 and sFGFR2Ap on the proliferation of MC3T3E1-Ap cells were analyzed by MTT assay.  To assess the effects of sFGFR2 and sFGFR2Ap on cell signaling pathways, the phosphorylation of ERK, p38, MEK, Shc, SAPK/JNK, PLCγ1 and Akt was examined by Western blotting.  The mineralized nodule formation with or without sFGFR2Ap was visualized by AR-S staining.

Results: Both sFGFR2 and sFGFR2Ap had inhibitory effects against the effect of FGF2 in osteoblasts proliferation and phosphorylation of ERK, p38, MEK, SAPK/JNK and Akt.  A mineralized nodule formation was strongly observed in the MC3T3E1-Ap. Addition of sFGFR2 and sFGFR2Ap suppressed mineralization of MC3T3E1-Ap as well as a MEK inhibitor (U0126) and a p38 inhibitor (SB203580).

Conclusions: Both sFGFR2 and sFGFR2Ap has inhibitory effect on proliferation,  differentiation and signaling cascade of osteoblastic cells in vitro.

Division: Japanese Division Meeting
Meeting: 2012 Japanese Division Meeting (Niigata, Japan)
Location: Niigata, Japan
Year: 2012
Final Presentation ID:
Abstract Category|Abstract Category(s): Scientific Program
Authors
  • Yoshizaki, Masako  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
  • Kobayashi, Yukiho  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
  • Moriyama, Keiji  ( Tokyo Medical & Dental University, Tokyo, N/A, Japan )
    • SESSION INFORMATION
    Craniofacial Biology