Role of tissue factor in diabetic osteoporosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09123
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Nara Medical University (2019-2020); Kindai University (2018)
• Principal Investigator: Tatsumi Kohei 奈良県立医科大学, 医学部, 准教授 (70555432)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病性骨粗鬆症 / 骨修復 / 組織因子 / 破骨細胞

Outline of Final Research Achievements

In this study, we examined the roles of tissue factor (TF) in delayed bone repair induced by diabetic state in mice using wild-type (WT) and low TF-expressing (LTF) mice. A diabetic state was induced by streptozotocin (STZ). A prolonged diabetic state significantly reduced bone mineral density (BMD) both in WT and LTF mice; these BMD parameters were similar between WT and LTF mice with or without STZ treatment. A diabetic state delayed bone repair following bone injury on the femoral bone in WT mice. Interestingly, a low level of TF was associated with further delay in bone repair in diabetes. In in vitro experiments, TF significantly decreased RANKL-induced osteoclast formation in RAW264.7 cells, whereas TF did not affect any gene expression levels in mouse primary osteoblasts. In conclusion, TF-induced suppression of bone remodeling might be involved in the protective effects of TF on delayed bone repair induced by a diabetic state.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症患者は年々増加しており、その有効な治療法の確立が急務である。骨粗鬆症の原因は様々だが、糖尿病などの生活習慣病を基盤とした骨粗鬆症の診療の重要性が近年認識されてきた。糖尿病性骨粗鬆症については、有効な診断・治療を可能とするためには、その病態を分子レベルで解明することが必須である。本研究は、血液凝固反応の起始因子である組織因子（TF）に焦点をあて、TFが有する新規の生理的役割としての観点から骨粗鬆症病態の一端を解明することに成功した。本研究の成果は、糖尿病患者の骨折治療において骨修復を促進せしめる新規治療法もしくは新薬の開発に向けての重要な基盤となる知見を提供するものと考えられる。