| Project/Area Number |
16K01924
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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 |
Biomolecular chemistry
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 骨軟骨 / 微小人工骨 / 再生治療 / ミトコンドリア / 軟骨分化 / 変形性関節症 / 低分子化合物 / MAPキナーゼ / 骨分化 / 骨軟骨分化 / ケミカルバイオロジー / プロテオミクス / 分化 |
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| Outline of Final Research Achievements |
Osteoarthritis (OA) is marked by loss of hyaline in the articular cartilage through stress-related injury, inflammation, or a genetic defect. However, the exact pathogenesis of OA is still not elucidated. Additionally, generally OA treatments provide only symptomatic relief. We found that TD-198946 (TD) strongly induced chondrogenic differentiation of progenitors without chondrocyte hypertorophy, which is also observed in OA. We previously identified M1 and M2, the mitochondrial proteins, as the candidates of TD target. In this research, we found that TD treatment facilitated the expression and cellular amount of M1, suggesting that the M1 expression was induced, along with the chondrogenic differentiation. We also discovered that TD promoted MAPK phosphorylation and M1 suppressed MAPK phosphorylation while M2 accelerated it. Finally, we improved the synthetic bone filler with regard to the efficient release of chondro-osoteogenic inducers.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性膝関節症の治療に関しては現在まで対症療法のみであり、我々がTDを利用することで実現を目指しているような、本質的な治療法 (関節軟骨の変性予防や修復・再生) は存在していなかった。また、これらのミトコンドリアタンパク質と変形性関節症治療を結びつけた研究は今までに無く、二重三重の意味で独創的だと考えている。
変形性膝関節症は高齢者の生活の質を低下させるロコモティブシンドロームの中でも最も重大な運動器変性疾患であり、画期的な原因治療薬の開発に繋げることができれば、痛みに苦しむ世界中の患者にとって大きな利益となるのは勿論のこと、国内の医療・製薬業界への波及効果も計り知れないと考えている。
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