| Project/Area Number |
16H05444
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高畑 雅彦 北海道大学, 医学研究院, 准教授 (40374368)
小野寺 智洋 北海道大学, 大学病院, 講師 (70547174)
前田 英次郎 北海道大学, 工学(系)研究科(研究院), 助教 (20581614)
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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 |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
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| Keywords | 関節病学 / 糖脂質 / 変形性関節症 |
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| Outline of Final Research Achievements |
We aimed to elucidate the molecular mechanisms of glycosphingolipids (GSLs) on chondrocytes involved in the development of osteoarthritis (OA) and to apply them to clinical treatment. In this project, various GSLs-related synthetase gene knockout mice (KO mice) are used to analyze the signal control function of each GSLs molecule against to IL-1 stimulation, and each of the GSLs existing upstream to downstream of GSLs biosynthetic pathway has been shown to be involved in the onset of OA. Moreover, we have clarified that severe OA develops when KO of GSLs molecule located more upstream. In addition, we have demonstrated that GSLs molecules have the function of controlling the transduction of stimulation into cells via Ca channels in response to mechanical stimulation on chondrocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
本プロジェクトではスフィンゴ糖脂質の中でもガングリオシドを部分的に欠損させると軟骨の肥大化・骨化が抑制され、軟骨修復過程に影響を及ぼすことが示唆された。また、それらのガングリオシド分子群を補充することでOA進行を予防が可能であることも明らかとした。これらの研究成果より、OA 発症および進行に関する GSLs の分子基盤の一部を解明し、疾患の制御および治療が可能となり得ることを明らかとした。
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