Novel mechanism leading to the death of hypertrophic chondrocytes in endochondral ossification through the regulation of CCN2 expression
| Project/Area Number |
19K19232
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | CCN2 / 軟骨 / 細胞死 / ROS / 内軟骨性骨化 |
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| Outline of Research at the Start |
内軟骨性骨化の最終段階（軟骨から骨への転化段階）－肥大軟骨細胞の細胞死については諸説あるが不明な点が多く、そのメカニズムを解明することは非常に重要である。
本研究では、「軟骨分化促進因子CCN2が、軟骨細胞内の活性酸素種(ROS)の量を制御して、軟骨細胞の細胞死を指揮する」という新たなメカニズムを解明する。
このメカニズムを解明できれば、骨・軟骨形成に異常をきたす疾病の原因・病態究明、治療法開発への貢献が期待できる。
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| Outline of Final Research Achievements |
The aim of this study was to investigate a novel mechanism that leads to the death of hypertrophic chondrocytes in endochondral ossification through the regulation of CCN2 expression. We found that CCN2 expression was up-regulated in low-concentration H2O2-treated chondrocytes but was down-regulated in high-concentration H2O2-treated ones. CCN2-silencing in chondrocytes induced apoptosis, and the induction of apoptosis was suppressed by a ROS inhibitor. These results suggest that CCN2 expression may be up-regulated by intracellular ROS rising during chondrocyte differentiation but finally down-regulated and thereby hypertrophic chondrocytes lead to ROS-mediated apoptosis.
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義：本研究により、内軟骨性骨化の最終段階―肥大軟骨細胞の細胞死誘導メカニズムの一端を解明する成果が生み出された。
社会的意義：本研究により、骨・軟骨形成に異常をきたす疾病の原因・病態究明、治療法開発につながる成果が生み出された。
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Report
(4 results)
Research Products
(1 results)
