| Project/Area Number |
18H05283
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section I
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| Research Institution | Nagasaki University |
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Principal Investigator |
Komori Toshihisa 長崎大学, 医歯薬学総合研究科(歯学系), 特命教授 (00252677)
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| Co-Investigator(Kenkyū-buntansha) |
姜 晴 長崎大学, 医歯薬学総合研究科(歯学系), 客員研究員 (00790007)
宮崎 敏博 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10174161)
森石 武史 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20380983)
松尾 友紀 長崎大学, 医歯薬学総合研究科(歯学系), 技術職員 (40792601)
川根 徹也 長崎大学, 医歯薬学総合研究科(歯学系), 客員研究員 (00265208)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥193,440,000 (Direct Cost: ¥148,800,000、Indirect Cost: ¥44,640,000)
Fiscal Year 2022: ¥32,760,000 (Direct Cost: ¥25,200,000、Indirect Cost: ¥7,560,000)
Fiscal Year 2021: ¥38,350,000 (Direct Cost: ¥29,500,000、Indirect Cost: ¥8,850,000)
Fiscal Year 2020: ¥39,260,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥9,060,000)
Fiscal Year 2019: ¥40,820,000 (Direct Cost: ¥31,400,000、Indirect Cost: ¥9,420,000)
Fiscal Year 2018: ¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
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| Keywords | 変形性関節症 / Runx2 / 軟骨細胞 / エンハンサー / 発現制御 / 細胞・組織 / 発生・分化 / 歯学 / 分化転換 / 血管進入 / アポトーシス / 骨芽細胞 / FGF / Wnt / ヘッジホッグ / オステオカルシン / Antxr1 / Hck |
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| Outline of Final Research Achievements |
We elucidated that a transcription factor Runx2 regulates the proliferation of osteoblast progenitor cells and their commitment to osteoblast-lineage cells through the induction of hedgehog, Fgf, Wnt, Pthlh signaling pathway genes, that Runx2 is required for the transdifferentiation of chondrocytes to osteoblasts, and that Runx2 regulates the expression of major bone matrix protein genes in osteoblasts. We also revealed that Osteocalcin, which expression is regulated by Runx2, aligns the apatite crystals parallel to collagen fibrils but it does not function as a hormone, although it was reported as a hormone. Runx2 is an essential transcription factor for chondrocyte maturation. We identified chondrocyte-specific enhancers in Runx2 genome locus and clarified the mechanism of the chondrocyte-specific expression.
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| Academic Significance and Societal Importance of the Research Achievements |
Runx2は、骨芽細胞分化・骨形成を制御するマスター転写因子であるが、Runx2による間葉系幹細胞から骨芽細胞への分化、その間の細胞増殖、軟骨細胞から骨芽細胞への分化転換、そして骨芽細胞分化後の機能制御の分子メカニズムを解明した。これは骨格形成の基礎となる知見である。また、オステオカルシンに関しては、これまで主要雑誌に多数報告されたホルモン作用を否定し、本来の機能を解明した。これまでの報告の問題点も指摘し、研究の流れを一新させた。骨芽細胞、軟骨細胞特異的エンハンサーによるRunx2遺伝子発現制御機構の解明は、骨格形成機構の基礎となるとともに、転写制御機構に新たな知見を与える。
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| Assessment Rating |
Ex-post Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, expected outcomes of research have been produced.
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Assessment Rating |
Interim Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.
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