| Project/Area Number |
18K06863
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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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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
河尾 直之 近畿大学, 医学部, 講師 (70388510)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨修復 / 糖尿病 / マクロファージ / 骨髄幹細胞 / PAI-1 / グルココルチコイド / 骨芽細胞 / 組織線溶 |
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| Outline of Final Research Achievements |
We investigate the role of macrophages in diabetic delayed bone repair after femoral bone injury in streptozotocin (STZ)- or dexamethasone (Dex)-treated and plasminogen activator inhibitor-1 (PAI-1)-deficient female mice. STZ- or Dex-treatment induced a significant delay in bone repair after bone injury in wild-type mice. PAI-1 deficiency significantly blunted Dex-induced delayed bone repair in mice. STZ- or Dex-treatment significantly decreased the numbers of macrophages at the damaged site on day 2 after femoral bone injury in mice. On the other hand, PAI-1 deficiency significantly attenuated a decrease in the number of macrophages induced by STZ- or Dex-treatment at the damaged site on day 2 after bone injury in mice. PAI-1 is involved in delayed bone repair after bone injury induced by type 1 diabetes or glucocorticoid in mice. PAI-1 may influence early stage osteoblast differentiation and apoptosis during the osteoblastic restoration phase of the bone repair process.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病で誘発される骨粗鬆症またはグルココルチコイド長期投与により誘発される糖尿病や骨粗鬆症は、骨折リスクを高める一要因とされている。しかし、その詳細な機序は不明であった。本研究では、マウスの異なるモデルを使用し、骨損傷後のマクロファージ低下を伴う修復遅延にPAI-1が関与することを示唆した。糖尿病やグルココルチコイドで誘発される骨修復遅延に対するPAI-1を標的として新たな治療法が期待される。
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