| Project/Area Number |
18K16668
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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 56020:Orthopedics-related
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| Research Institution | Hokkaido University (2019-2021)
Sapporo Medical University (2018) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 手根管症候群 / 細胞老化 / 滑膜下結合組織 / 線維化 / 滑膜 / ドラッグリポジショニング |
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| Outline of Final Research Achievements |
Carpal tunnel syndrome (CTS) is the most common compression neuropathy. Effective treatments are limited to surgical interventions, and novel treatments have not yet been developed. In CTS patients, fibrosis of the subsynovial connective tissue surrounding the median nerve in the carpal tunnel is known as a pathological condition that compresses the median nerve in the carpal tunnel. In this study, we investigated cellular senescence in subsynovial connective tissue in CTS. In the CTS patients, PDGFRa + cells expressed both senescence factors and the macrophage checkpoint. PDGFRa + senescent cells avoided the phagocytosis of macrophages. Furthermore, PDGFRa+ senescent cells promoted the proliferation of adjacent fibroblasts. When senescent fibroblasts were transplanted into the carpal tunnel of a rabbit model, an increase in fibrosis-related genes was observed in the subsynovial connective tissue. Finally, one of senolytics induced apoptosis in PDGFRa + rather than control cells.
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| Academic Significance and Societal Importance of the Research Achievements |
CTSは中高年の10人に1人が発症するとされるものの、その原因は未だ明らかでなく、有効な治療は外科介入に限られている。本研究によりCTS患者に対する新たな内科的治療法が明確になれば、世界中の患者に迅速に届けられる、低侵襲で安価かつ安全な治療法となり、学術的および社会的意義は大きい。
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