Elucidation of macrophage function and abnormal of bone marrow stem cells in delayed bone repair in diabetic mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06863
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kindai University
• Principal Investigator: OKADA Kiyotaka 近畿大学, 医学部, 教授 (20185432)
• Co-Investigator(Kenkyū-buntansha): 河尾 直之 近畿大学, 医学部, 講師 (70388510)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨修復 / 糖尿病 / マクロファージ / 骨髄幹細胞 / PAI-1

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.

Free Research Field

医歯薬学

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。