成骨和成血管是骨缺损修复过程中必不可缺的两个重要过程。探究成骨和成血管过程相互协同作用的内在机制是改善骨移植替代物的血管化程度从而促进骨缺损修复的关键科学问题。其中近分泌途径可能是间充质干细胞和血管内皮细胞相互调控作用中的重要方式，目前关于近分泌途径的具体机制仍不清楚。EphrinB2/EphB4是受体酪氨酸激酶家族中的一对传导双向信号的膜蛋白，它可以通过近分泌方式分别调控成骨和成血管。但是还未出现EphrinB2/EphB4双向信号对成骨和成血管耦合调控的报道。因此，本课题拟研究EphrinB2/EphB4双向信号分子在间充质干细胞/血管内皮细胞近分泌调控中的相关性并阐明具体下游信号网络，探讨EphrinB2/EphB4双向信号分子作为促进骨组织再生中成骨成血管协同调控靶点的可行性。本项目研究有助于实现对成骨成血管过程的调控，从而促进血管化组织工程骨修复骨缺损的临床转化。

The recently proposed strategy that vascularization of bone tissue engineering increases the possibility of repairing complicated bone defect cases by using bone graft substitutes prepared via tissue engineering techniques. Studying the cellular interactions between two kinds of seed cells (bone marrow stem cells and endotheilial cells, BMSCs and ECs) is one of the vital issues to promote the vascularization of bone tissue engineering. Juxtacrine is an important part of these cellular interactions, but until now, researchers still don’t know how it works. EphrinB2 / EphB4 bidirectional signal has been documented as a regulator of osteoblast/osteoclast communication or angiogenesis process under the effect of juxtacrine, whereas there is little research about its role in the process of osteogenesis/angiogenesis crosstalking. Therefore, in this study we plan to reveal the role of EphrinB2/ EphB4 bidirectional signal in regulating BMSCs/ECs interactions and the corresponding downstream signaling pathways under the effect of juxtacrine. Moreover, we try to define the feasibility of EphrinB2/ EphB4 bidirectional signal as a potential target for coordinated regulation of osteogenesis/angiogenesis crosstalking. Finally, this study may help to precisely modulate the process of osteogenesis/angiogenesis crosstalking and then promote the clinical transformation of vascularization of bone tissue engineering.