Investigating the role of RUNX2 in osteoblastic differentiation of mouse and human iPSCs
Project/Area Number |
18K17056
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 57030:Conservative dentistry-related
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Research Institution | Tokyo Dental College |
Principal Investigator |
Aoki Hideto 東京歯科大学, 歯学部, 助教 (90801481)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | Runx2 / iPS細胞 / 骨芽細胞分化 |
Outline of Final Research Achievements |
This study aimed to establish iPSCs from Runx2 homo-deficient (Runx2-/-) mouse and to elucidate the role of RUNX2 in the differentiation process into osteoblasts. Furthermore, we investigate the difference in the mechanisms involved in osteoblastic differentiation, in mouse iPSCs and human iPSCs. A later stage marker of osteogenesis were significantly lower in Runx2-/- miPSCs than in wild-type and Runx2+/- miPSCs, suggesting that osteoblastic differentiation will not proceed to later stages in Runx2-/- miPSCs. A total of 53 genes were downregulated and only three genes were upregulated in Runx2-/- miPSCs compared with wild-type miPSCs. We also confirmed that expression of genes by osteoblastic differentiation from human iPSCs suggesting that the function of Runx2 confirmed in the mouse model is the same in humans. Our finding will have implications for improving our understanding of RUNX2 functions in bone formation.
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Academic Significance and Societal Importance of the Research Achievements |
iPS細胞は多分化能を有することで再生医療の重要なソースとして注目されている。その応用には効率的かつ安全性の高い分化誘導法の確立が必須とされている。しかしながら、iPS細胞から種々の細胞への分化誘導における詳細なメカニズムは不明な点が多く、その一端が解明されたと考える。本研究では疾患特異的iPS細胞のマウスモデルとヒトでの検討を行い、その類似点や相違点を解析した。これは、マウスモデルの解析の重要性が示されたことにもつながると考える。これらの内容はRunx2欠損をはじめとする多くの遺伝子疾患にとっての病態解明や創薬にもつながる重要なデータである。
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Report
(4 results)
Research Products
(2 results)