肠道菌群具有调控骨代谢的功能已经被证实，然而其机制及相关信号通路仍未阐述清楚，认识这一机制对临床治疗骨折延迟愈合、骨折不愈合等一系列临床难题具有重要意义。有研究表明，骨折愈合与神经纤维长入密切相关，神经生长导向因子Semaphorin 3A (Sema 3A)，可通过调控感觉神经纤维长入调节骨量代谢。我们前期研究结果发现：Sema 3A具有促进骨折愈合的效果。有研究证实肠道菌群对Sema3A具有调控作用。提示：肠道菌群可通过调控Sema 3A蛋白促进骨折愈合。.在此基础上，我们提出本课题设计：1、肠道菌群能否通过调控Sema 3A及其相关受体而影响骨折愈合过程？2、该效应涉及的信号通路是什么？传统调控成、破骨细胞分化的经典信号通路与该通路有何关系？3、是否存在某种特异性肠道菌群差异，能够产生促进骨折愈合的作用？以期阐明肠道菌群在骨折加速愈合中的作用和机制，为骨折不愈合的治疗提供新的思路。

The function of gut microbiota regulating bone metabolism has been proven, but its mechanism and related signaling pathways have not been elucidated clearly. Understanding this mechanism is of great significance for clinical treatment of a series of clinical difficulties such as delayed union or nonunion of fracture. Studies have shown that fracture healing is closely related to nerve fiber ingrowth. Sema 3A can promote bone metabolism by regulating sensory nerve fiber ingrowth. Our previous research found that Sema 3A has the effect of promoting fracture healing. Studies have confirmed that the gut microbiota can regulate Sema 3A. So, we hypothesize that the microbiota can promote fracture healing by regulating the Sema 3A..Based on this, we propose the design of this research: 1. Can the gut microbiota affect the fracture healing process by regulating Sema 3A and its related receptors? 2. What is the signal pathway involved in this effect? What is the relationship between the classical signaling pathway that traditionally regulates osteoclast differentiation? 3. Is there a difference in specific microbiota that can promote fracture healing? The aim of this research is to clarify the role and mechanism of gut microbiota in accelerated fracture healing, and provide new ideas for the treatment of nonunion.