| Project/Area Number |
16K08476
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
Ikeda Yayoi 愛知学院大学, 歯学部, 教授 (00202903)
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| Co-Investigator(Kenkyū-buntansha) |
池田 正明 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (20193211)
三谷 章雄 愛知学院大学, 歯学部, 教授 (50329611)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | エストロゲン / 骨代謝 / ノックアウトマウス / 細胞・組織 / 発生・分化 / 発現制御 |
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| Outline of Final Research Achievements |
The orphan nuclear receptor steroidogenic factor 1 (SF-1) is expressed in both Sertoli and Leydig cells in testes. We generated conditional knockout (cKO) mice, in which SF-1 was specifically inactivated in the brain using Cre-loxP recombination with Nestin-Cre. Expression levels of SF-1 were specifically lower in the brain of the brain-specific SF-1 KO mice compared with wild-type controls, whereas those in the testis or the adrenal gland were similar between the two genotypes. The body weight was apparently lower in the brain-specific SF-1 KO mice than in wild-type controls during postnatal development. Micro-CT analysis showed that bone mineral density was increased in both the trabecular and cortical bone compartments in brain-specific SF-1 KO mice compared with controls. The results indicate that inactivation of central SF-1 signaling results in increased bone mass, suggesting that central inhibitory SF-1 actions are involved in the regulation of bone mass.
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| Academic Significance and Societal Importance of the Research Achievements |
エストロゲン骨への作用が末梢と脳で異なり、その分子機構にSF-1が関与することが示唆され、エストロゲンの骨代謝制御の分子機構研究において新たな展開となり、解明に大きく貢献できる。エストロゲン欠如による骨粗鬆症は、歯周病悪化を引き起こし、口腔領域の治療に大きく影響するものである。本研究成果は、骨粗鬆症のエストロゲン補填療法で使用されるエストロゲン製剤として、脳でのエストロゲンの作用を抑え、より強力な治療効果をもつ新薬開発の基礎データとしての意義がある。
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