骨质疏松性骨折愈合慢，病程长，是老年患者中致残致死率较高的疾病，临床上缺乏有效促进骨折愈合的常规药物。骨髓间充质干细胞（bMSC）在骨折急性期增殖，随后分化而发挥骨形成作用；激活Notch通路可促进bMSC增殖，抑制Notch信号通路则可以促进bMSC分化。本项目拟针bMSC中的Notch信号通路，形成促进质疏松性骨折愈合的综合治疗方案：1）前期已发现利用Jag1重组蛋白激活体外培养的bMSC中的Notch信号通路，可以有效促进bMSC增殖，本项目拟在骨松骨折早期体内注射Jag1重组蛋白，调动内源性bMSC增殖，储备足够的bMSC；2）在前期基础上，证明优化的化瘀补肾方可以促进骨质疏松小鼠骨折愈合，并进一步筛选化瘀补肾方中可以抑制Notch信号通路、促进bMSC骨形成的有效组分并组合，在骨折急性型期过后通过微型渗透泵局部缓释有效组分，从而促进骨质疏松性骨折愈合。

Osteoporotic fracture is the disease of high morbidity and mortality among the elderly people due to the delayed fracture healing process and prolonged course of disease. Bone marrow mesenchymal stem cells (bMSCs) can proliferate in the acute inflammatory phase of bone fracture and differentiate in the later phases to promote bone formation. Notch signaling pathway becomes one of the potential regulation targets to promote fracture healing because of its important role in regulation bMSC proliferation and differentiation. In this project, the staged treatment of osteoporotic fracture healing will be studied from the point of Notch signaling pathway in bMSCs. 1) Previously we found that Jag1 recombinant protein stimulated bMSC proliferation and maintained MSC properties in vitro. In this study, Jag1 will be directly injected into mice model of osteoporotic fracture to promote endogenous bMSC proliferation at the early stage of fracture healing. 2) We will also confirm that Huayu Bushen Formula can promote fracture healing in mice with osteoporosis, and screen more inhibitors of Notch signaling pathway from the effective components of Huayu Bushen Formula to enhance bMSC differentiation and bone formation. The combined effective components will be delivered by an osmotic minipump locally in a sustained fashion after the acute inflammatory phase of bone fracture to accelerate bone formation.