Role of Runx2 in bone remodeling induced by mechanical stress in the animal model of Cleidocranial dysplasia
| Project/Area Number |
18K09827
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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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| Review Section |
Basic Section 57070:Developmental dentistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 照子 東北大学, 歯学研究科, 名誉教授 (00127250)
北浦 英樹 東北大学, 歯学研究科, 准教授 (60295087)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 歯の移動 / Runx2 / 機械的刺激 |
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| Outline of Final Research Achievements |
Cleidocranial dysplasia (CCD) is caused by mutations of RUNX2, and orthodontic treatment for CCD patients is difficult because of impaired tooth movement. We examined the amount of experimental tooth movement in Runx2+/- mice, the animal model of CCD, and continuous stretch was conducted to bone marrow stromal cells (BMSCs). Compared to wild-type the Runx2+/- mice exhibited delayed experimental tooth movement, and osteoid formation were impaired on the tension side of tooth movement. Runx2+/- BMSCs decreased stretch-induced proliferation. Furthermore, mTORC2 is regulated by Runx2 to phosphorylate Akt to regulate cell proliferation and differentiation. Runx2+/- mice exhibited delayed and suppressed expression of mTOR and Rictor in osteoblasts on the tension side of tooth movement. Runx2+/- BMSCs inhibited stretch-induced PI3K dependent mTORC2/Akt activity to promote BMSCs proliferation. mTORC2 regulated stretch-elevated Runx2 and ALP mRNA expression in BMSCs in osteogenic medium.
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| Academic Significance and Societal Importance of the Research Achievements |
Runx2ヘテロ欠損マウスの矯正学的歯の移動モデルは機械的刺激による骨リモデリングのRunx2の解析に有用であり、Runx2によるmTORC2活性化は伸展力による骨芽細胞系細胞の増殖および骨分化機構に重要な役割をはたすことが示唆された。これらの研究成果は、鎖骨頭蓋異形成症患者の歯の移動遅延メカニズムの解明に繋がり、さらに同症患者の矯正歯科治療に貢献できると考えられる。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application.2018
Author(s)
Ida H, Seiryu M, Takeshita N, Iwasaki M, Yokoyama Y, Tsutsumi Y, Ikeda E, Sasaki S, Miyashita S, Sasaki S, Fukunaga T, Deguchi T, Takano-Yamamoto T.
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Journal Title
Acta Biomater.
Volume: 74
Pages: 505-517
DOI
Related Report
Peer Reviewed / Open Access
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