| Project/Area Number |
16K10908
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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 |
Orthopaedic surgery
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
久木田 明子 佐賀大学, 医学部, 准教授 (30153266)
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| Research Collaborator |
Shiraki Makoto
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 破骨細胞 / 転写因子 / 骨代謝 / ストレス / 分化 / 核タンパク質 / 骨吸収 / オートファジー / アポトーシス / 骨・軟骨代謝 |
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| Outline of Final Research Achievements |
HMG-related protein nuclear protein 1 (NUPR1/p8) is a multifunctional stress-induced protein involved in regulating tumorigenesis, apoptosis, and autophagy. We analyzed expression and role of Nupr1 in osteoclastogenesis. Nupr1 was induced by RANKL in osteoclast differentiation. Using micro-computed tomography, we found that mice lacking Nupr1 exhibited increased bone volume. Histological analysis showed that Nupr1 deficiency decreased osteoclast numbers. In vitro culture of bone marrow macrophages showed that RANKL-induced osteoclastogenesis was downregulated, and cell proliferation was decreased in Nupr1-deficient of osteoclast precursor cells. In addition, expression of autophagy-related genes were upregulated, whereas apoptosis induced by autophagy was enhanced in Nupr1-deficient osteoclasts. These results indicate that Nupr1 is a novel regulator of bone volume by promoting the growth of osteoclast precursor and survival of osteoclasts.
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| Academic Significance and Societal Importance of the Research Achievements |
骨代謝は骨吸収を行う破骨細胞と骨形成を行う骨芽細胞によって営まれており、炎症や栄養状態、ストレスなどによっても影響を受ける。Nupr1 はストレスで誘導されストレス応答のキープレイヤーとして注目されており、癌細胞の増殖や進展においても重要な働きをすることが報告されている。本研究では、初めてNupr1が生理的条件下での破骨細胞の分化と骨量の維持において新らたな働きをしていることを明らかにした。本研究で得た知見は、骨破壊を伴う骨関連疾患の理解や治療法の開発などの研究に将来的に寄与するものと考えられる。
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