| Project/Area Number |
18H03007
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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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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中村 貴 東京歯科大学, 歯学部, 講師 (80431948)
柴原 孝彦 東京歯科大学, 歯学部, 教授 (50178919)
齋藤 淳 東京歯科大学, 歯学部, 教授 (60266559)
小野寺 晶子 東京歯科大学, 歯学部, 講師 (90637662)
齋藤 暁子 東京歯科大学, 歯学部, 助教 (90722835)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
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| Keywords | GNAS / ヘッジホッグ / iPS細胞 / 骨芽細胞 / 骨 / 線維性骨異形成症 / McCune Albright 症候群 / 消化管腫瘍 / GPCR / Gorlin症候群 / McCuneAlbright症候群 / Hedgehog経路 / 骨代謝 / 骨粗しょう症治療薬 / cAMP / Hedgehog / iPS / 石灰化 / ｃAMP / マキューンオルブライト症候群 / ヘッジホッグ経路 / GANS / McCune Albright Syndrome |
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| Outline of Final Research Achievements |
The pathophysiology of congenital skeletal diseases is diverse, and it has been clarified that disease-specific iPS cell application is important for elucidating the pathophysiological mechanism of the disease. GNAS-rich iPS cells (fibrous dysplasia and McCune-Albright syndrome) iPS cells were generated and compared with Gorlin syndrome ipS cells, with the aim of elucidating the relationship and pathophysiology of the Hedgehog pathway and the GNAS pathway. When GNAS-rich iPS cells were established and neoplastic lesions were reproduced, it was found that the undifferentiated state of diseased cells was enhanced. Therefore, it was clarified that the inhibition of osteoblast differentiation in fibrous dysplasia may be directly linked to the treatment by appropriately correcting the inhibition of Hedgehog by drug administration.
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| Academic Significance and Societal Importance of the Research Achievements |
GNAS過剰変異は Sporadicに発生するMcCuneAlbright syndrome や Fibrous dysplasia など にみられる遺伝子変異であるが その解明においては 上記疾患細胞の獲得が非常に困難であることが 大きな障害となっていた。 本研究にて iPS細胞を作製したことにより この疾患に関連した多くの疾患（線維性骨異形成症、消化管良性腫瘍 膵癌）の研究など広範に利用可能である、
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