骨折血肿微环境对骨愈合具有重要的调控作用，但其促进骨愈合的机制尚未阐明。申请者前期研究发现乳脂肪球表皮生长因子8蛋白（MFG-E8）在骨折血肿炎症微环境中表达显著升高，并可促进骨髓间充质干细胞（BMSCs）成骨分化。进一步探索发现外源性MFG-E8可上调GSK3β磷酸化水平，同时下调Rac1水平和p-IκBα水平从而影响BMSCs成骨分化。据此，我们提出假说：在血肿炎症微环境中，MFG-E8通过调控p-GSK3β、Rac1水平和NF-κB信号通路促进BMSCs成骨分化。本课题拟在上述研究基础上，从整体、细胞和分子水平，探讨MFG-E8促进血肿炎症微环境中BMSCs成骨分化的可能分子机制，为丰富骨折不愈合和骨缺损的治疗提供学术依据。

Microenvironment of fracture hematoma plays an important role in the regulation of bone healing, but the mechanisms of promoting bone healing have not been elucidated yet. Our preliminary study found that the expression of the milk fat globule-derived epidermal growth factor 8 protein (MFG-E8) in the inflammation of fracture hematoma was significantly increased and the osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) was promoted. Further exploration found that MFG-E8 can up-regulate the phosphorylation of GSK3β and downregulate the Rac1 and p-IκBα level，influencing the osteogenic differentiation of BMSCs. Accordingly, we hypothesize that MFG-E8 promotes osteogenic differentiation of BMSCs through regulation of p-GSK3β, Rac1 levels and NF-κB pathway in the inflammatory microenvironment of fracture hematoma. Based on the above studies, this study intends to explore the possible molecular mechanisms of MFG-E8 in promoting the osteogenic differentiation of BMSCs in the inflammatory microenvironment of fracture hematoma, and provides an academic basis for the treatments of fracture nonunion and bone defects.