| Project/Area Number |
17K19737
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
IRIE Atsushi 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主任研究員 (10280786)
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| Project Period (FY) |
2017-06-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 破骨細胞 / 細胞融合 / siRNA / 脂質 |
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| Outline of Final Research Achievements |
Osteoclasts, responsible for bone resorption, are formed by cell-cell fusion of mononuclear pre-osteoclasts. We have found that rearrangement of phosphatidylethanolamine (PE) in the plasma membrane is increased during osteoclastogenesis. Although the PE dynamics in cell-cell fusion were also observed in other cell fusion phenomena, e.g., myoblasts and multinuclear macrophages, their redistribution of PE was less effective than that was detected in osteoclasts. These results suggest that the PE dynamics required for cell-cell fusion in osteoclasts are unique for osteoclastogenesis. In addition, we have developed a new strategy for siRNA stabilisation for future application of the lipid-related molecules involved in osteoclast fusion. We have found that an artificial cationic oligosaccharide combined with phosphorothioate linkages strongly improves siRNA stability.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、破骨細胞と破骨細胞以外の細胞融合系の脂質動態について比較した初めての研究であり、本研究によって、それぞれの融合系は脂質動態に関して異なった機構を用いている可能性が高いことが示唆された。今後、破骨細胞特異的な脂質動態に焦点をあてて研究を発展させることが、破骨細胞融合機構のさらなる解明につながるものと考えられる。また、本研究によってsiRNAの新しい安定化手法が見出された。核酸医薬品は、新しい世代の創薬ツールとして注目されているが、生体内における安定性という点では改善すべき点が多い。本研究はsiRNA医薬品の安定化の一助になる可能性があり、新しい骨代謝疾患治療薬への応用が期待できる。
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