Department of Physiology and Regenerative Medicine, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
Advanced Medical Science of Thrombosis and Hemostasis, Nara Medical University, Kashihara, Nara, Japan.
PLoS One. 2021 Dec 2;16(12):e0260754. doi: 10.1371/journal.pone.0260754. eCollection 2021.
Tissue factor (TF) is the primary activator of the extrinsic coagulation protease cascade. Although TF plays roles in various pathological states, such as thrombosis, inflammatory diseases, cancer, and atherosclerosis, its involvement in bone metabolism remains unknown.
The present study examined the roles of TF in delayed bone repair induced by a diabetic state in mice using wild-type (WT) and low TF-expressing (LTF) male mice. A diabetic state was induced by intraperitoneal injections of streptozotocin (STZ).
A prolonged diabetic state significantly reduced total and trabecular bone mineral densities (BMD) as well as cortical bone thickness in WT and LTF mice; these BMD parameters were similar between WT and LTF mice treated with or without STZ. The diabetic state induced in WT mice delayed the repair of the femur following injury. The diabetic state induced in LTF mice was associated with further delays in bone repair. In in vitro experiments, TF significantly decreased receptor activator of nuclear factor-κB ligand-induced osteoclast formation and osteoclastogenic gene expression in RAW264.7 cells. However, it did not affect the gene expression levels of runt-related transcription factor 2 and osterix as well as alkaline phosphatase activity in mouse primary osteoblasts.
Low TF state was associated with enhanced bone repair delay induced by diabetic state in mice. The TF-induced suppression of bone remodeling may be a contributing factor to the protective effects of TF against delayed bone repair in a diabetic state.
组织因子 (TF) 是外源性凝血蛋白酶级联反应的主要激活剂。尽管 TF 在各种病理状态下（如血栓形成、炎症性疾病、癌症和动脉粥样硬化）发挥作用，但它在骨代谢中的作用仍不清楚。
本研究使用野生型 (WT) 和低 TF 表达 (LTF) 雄性小鼠，研究了 TF 在糖尿病状态下诱导的小鼠延迟骨修复中的作用。通过腹腔注射链脲佐菌素 (STZ) 诱导糖尿病状态。
长期糖尿病状态显著降低 WT 和 LTF 小鼠的总骨和小梁骨骨密度 (BMD) 以及皮质骨厚度；WT 和 LTF 小鼠在有无 STZ 处理下，这些 BMD 参数相似。WT 小鼠的糖尿病状态延迟了损伤后股骨的修复。LTF 小鼠的糖尿病状态与骨修复的进一步延迟有关。在体外实验中，TF 显著降低了核因子-κB 配体激活的破骨细胞形成和破骨细胞生成基因表达在 RAW264.7 细胞中。然而，它不影响小鼠原代成骨细胞中 runt 相关转录因子 2 和骨钙素的基因表达水平以及碱性磷酸酶活性。
低 TF 状态与糖尿病状态下小鼠骨修复延迟增强有关。TF 诱导的骨重塑抑制可能是 TF 对糖尿病状态下延迟骨修复的保护作用的一个因素。
