| Project/Area Number |
17K11035
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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 |
Orthopaedic surgery
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Yudo Kazuo 聖マリアンナ医科大学, 医学研究科, 教授 (60272928)
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| Co-Investigator(Kenkyū-buntansha) |
油井 直子 聖マリアンナ医科大学, 医学部, 講師 (20266696)
唐澤 里江 聖マリアンナ医科大学, 医学研究科, 准教授 (50434410)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 変形性関節症 / 軟骨代謝 / メカニカルストレス / 細胞エネルギー代謝 / 軟骨細胞 / エネルギー代謝 / 核酸修復酵素 / ストレス応答能 / NAD依存性脱アセチル化酵素活性 / ストレス応答蛋白 / 核酸損傷修復酵素 / 軟骨変性 |
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| Outline of Final Research Achievements |
Mechanical stress is a critically-important factor affecting bone tissue homeostasis. To determine whether physiologic mechanical loading affects the expression of factors regulating energy metabolism and transcription factors controlling chondrocyte differentiation, we focused on the interaction among mechanical stress, DNA repair enzymes and the cellular energy sensor sirtuin 1 (SIRT1) in cellular energy metabolism, since it has been recognized that SIRT1, an NAD+-dependent deacetylase, may function as a master regulator of mechanical stress response as well as cellular energy metabolism.
To further understand the involvement of sirtuins in the “cellular metabolism” and “stress tolerance” is conductive to the new insights into the pathophysiology and the development of novel therapies for a variety of osteoarthritis. We demonstrated the critical important roles of sirtuins in the cellular metabolism and response to mechanical stresses in osteoarthritic chondrocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、変形性関節症の発症に密接に関わるメカニカルストレスに対する軟骨細胞の応答機構の分子メカニズムに着目し、軟骨変性機序との関連について解明を試みる初めての基礎的研究で、軟骨変性の機序を「軟骨細胞のメカニカルストレス応答」と、「DNA損傷修復」および「エネルギー代謝」との関連の観点から詳解し、新規の病因・病態解析および予防・治療法開発研究の糸口を得られた。
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