糖尿病足是糖尿病常见而又严重的并发症之一，下肢周围动脉病变是糖尿病足溃疡截肢的主要风险因素。OPG/RANKL/RANK系统与胰岛细胞增殖及肝脏胰岛素抵抗相关，参与糖尿病发病。OPG/RANKL/RANK系统与缺血性动脉疾病和糖尿病下肢周围动脉病变密切相关。我们前期研究发现，和野生型小鼠相比，OPG基因敲除（OPG-/-）小鼠股动脉结扎后，下肢血流恢复减慢，血管新生受损，下肢缺血损伤更严重。本研究在动物水平，研究外源性重组OPG、OPG过表达和RANKL抑制剂（Denosumab）对糖尿病小鼠股动脉结扎后血管新生和缺血损伤的影响；采用小鼠内皮祖细胞（EPC)和人脐带血管内皮细胞（HUVEC），研究OPG/RANKL/RANK系统对小鼠EPC和HUVEC增殖、凋亡、迁移和管腔形成的影响；采用单细胞测序深入探讨信号通路；揭示糖尿病足发病新机制，为糖尿病足防治提供新的作用靶点。

Diabetic foot is one of the common and severe complications of diabetes and the leading cause of amputation. Peripheral artery disease of lower extremity is the main risk factor of diabetic foot ulcer amputation. The OPG/RANKL/RANK system is associated with islet cell proliferation and hepatic insulin resistance, and is involved in the pathogenesis of diabetes. OPG/RANKL/RANK system is closely related to ischemic arterial disease and diabetic peripheral artery disease of lower extremity. Our previous study showed that compared with wild-type mice，the OPG knockout mice had slower recovery rate of lower extremity perfusion and more severe ischemic injury with impaired angiogenesis after femoral artery ligation. In this study, exogenous recombinant OPG, OPG overexpression and RANKL inhibitor (Denosumab) were used to explore their effects on angiogenesis and ischemic injury after femoral artery ligation in diabetic mice. Mouse endothelial progenitor cells (EPC) and human umbilical cord vascular endothelial cells (HUVEC) were used to investigate the effects of OPG/RANKL/RANK system on the proliferation, apoptosis, migration and tube formation of these cells in mice. Microwell-Seq single cell was adopted to sequence to explore the signaling pathway. We aim to reveal new pathogenesis of diabetic foot and provide new target for prevention and treatment of diabetic foot.