Project/Area Number |
18K11019
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Mie University |
Principal Investigator |
ITOH Tomohiro 三重大学, 生物資源学研究科, 准教授 (30435854)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | メカニカルストレス / 骨細胞 / 破骨細胞分化 / 膜小胞 / 骨代謝 / マイクロRNA / CD9 / CD63 / ショットガンプロテオーム解析 / エクソソーム / 破骨細胞 / 分化 / 膜微小胞 |
Outline of Final Research Achievements |
Osteocyte, which is the most abundant cell in bone tissues, is well known as a mechanical stress (MS) receiving cell. During bone remodelling, bone resorption by osteoclasts precedes bone formation by osteoblasts. However, its mechanism is still unknown. In this study, we examined whether exosome released from osteocyte by MS stimulation are involved in osteoclast differentiation. Though the vesicles isolated from mechanical stress-loaded MLO-Y4 cells had no effect against osteoblast differentiation, these vesicles significantly induced osteoclast differentiation. To characterize the mechanisms by which mechanical stress-loaded MLO-Y4 cell vesicles induces osteoclast differentiation in murine macrophage RAW264.7 cells, we analysed vesicle membrane and vesicle internal proteins by nano-LC-MS/MS-based shotgun proteomics. As a result, Protein X , CD9 and CD63 were only detected in mechanical stress-loaded MLO-Y4 cell vesicles.
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Academic Significance and Societal Importance of the Research Achievements |
私たちが日常の生活活動する中で起きる骨代謝の基本機構である「まず骨が壊され,新しい骨が作られる」というホメオスタシス機構について様々な知見が報告されているが,未解明なところが多い。本研究では,成長期の体重増によるメカニカルストレスを受けた際の骨代謝時に骨細胞から分泌される膜小胞が深く関与していることを示すことができ,骨のホメオスタシス機構の一機構を明らかにできた点で学術的意義があった。また,骨代謝における膜小胞の役割(機能)を見出すことで,超高齢化社会の中で増える骨粗鬆症患者への治療薬への応用利用など発展性が期待できた点では社会的意義ある研究成果を導くことができたと考える。
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