| Project/Area Number |
23390471
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthodontic/Pediatric dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MORIYAMA Keiji 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (20262206)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Takuya 東京医科歯科大学, 大学院・医歯(薬)学総合研究科, 講師 (50401360)
HIGASHIHORI Norihisa 東京医科歯科大学, 大学院・医歯(薬)学総合研究科, 助教 (50585221)
KOBAYASHI Yukiho 東京医科歯科大学, 大学院・医歯(薬)学総合研究科, 助教 (20596233)
AKIYOSHI Kazunari 京都大学, 工学部, 教授 (90201285)
大隈 瑞恵 東京医科歯科大学, 歯学部, 非常勤講師 (60456209)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | 歯学 / 頭蓋冠縫合部早期癒合症 / ナノサイエンス / アペール症候群 / FGFR2 / 可溶型受容体 / Apert症候群 / 先天異常 / 骨芽細胞分化 |
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| Research Abstract |
Here we aimed to clarify the etiological mechanisms of craniosynostosis in mouse models of Apert syndrome and verify the effects of purified soluble FGFR2 harboring the S252W mutation (sFGFR2IIIcS252W) on calvarial sutures in Apert syndrome mice in vitro. We observed increased expression of Fgf10, Esrp1, and Fgfr2IIIb, which are indispensable for epidermal development, in coronal sutures in Apert syndrome mice. Purified sFGFR2IIIcS252W exhibited binding affinity for Fgf2 but also formed heterodimers with FGFR2IIIc, FGFR2IIIcS252W, and FGFR2IIIbS252W. sFGFR2IIIcS252W complexed with nanogels maintained the patency of coronal sutures, whereas synostosis was observed where the nanogel without sFGFR2S252W was applied. Thus, based on our current data, we suggest that increased Fgf10 and Fgfr2IIIb expression may induce the onset of craniosynostosis in patients with Apert syndrome and that the appropriate delivery of purified sFGFR2IIIcS252W could be effective for treating this disorder.
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