Abstract Number: LPB0023
Meeting: ISTH 2021 Congress
Background: Tissue factor (TF) is the primary activators of the extrinsic coagulation protease cascade. Although TF is related to various pathological states, the roles of TF in bone metabolism are unknown.
Aims: To examine the roles of TF in delayed bone repair induced by diabetic state in mice using wild-type (WT) and low TF-expressing (LTF) mice.
Methods: Diabetes was induced by daily intraperitoneal injections of streptozotocin at a dose of 50 mg/kg BW for 4 days. Mice with blood glucose levels greater than 300 mg/dL were considered diabetic. At 2 weeks after confirming the induction of diabetes, a bone defect surgery was performed in the right femur of the mice. The repair of the defect was serially monitored with quantitative computed tomography (qCT).
Results: A prolonged diabetic state significantly reduced total and trabecular bone mineral density (BMD) as well as cortical bone thickness 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 LTF state was associated with further delay in bone repair in diabetes. In in vitro experiments, TF significantly decreased receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast formation and osteoclastogenic gene expression in RAW264.7 cells. On the other hand, TF did not affect the gene expression levels of runt-related transcription factor 2 (Runx2) and Osterix as well as alkaline phosphatase activity in mouse primary osteoblasts.
Conclusions: LTF state is associated with enhanced bone repair delay induced by diabetic state in mice. Moreover, TF suppressed osteoclast formation in vitro. TF-induced suppression of bone remodeling might be involved in the protective effects of TF on delayed bone repair induced by a diabetic state.
To cite this abstract in AMA style:Tatsumi K, Ehara H, Takafuji Y, Kawao N, Ishida M, Okada K, Mackman N, Shima M, Kaji H. Role of Tissue Factor in Delayed Bone Repair Induced by Diabetic State in Mice [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/role-of-tissue-factor-in-delayed-bone-repair-induced-by-diabetic-state-in-mice/. Accessed November 28, 2022.
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