骨移植修复颌骨常发生术后疏松化但无有效预防方法。我们前期研究发现神经通过递质调控骨髓间充质干细胞（BMMSC）的动员和分化，提出的神经化骨瓣新方法明显减少移植骨疏松化。Sema3A参与神经调控并影响骨改建，但其干细胞机制不明。据此提出假说：神经源性Sema3A结合于BMMSC表达的Nrp1，经由WNT通路调控nrp1等基因，增加Nrp1蛋白表达，形成正反馈环路强化Sema3A促进BMMSC活力的作用。我们拟通过干细胞分离及与背根节共培养、动物实验及临床标本等，验证Sema3A与BMMSC活力的相关性，探讨Sema3A/Nrp1/WNT正反馈环增强BMMSC活力的分子机制，进一步在下颌骨失神经和Sema3A KO小鼠模型进行体内验证，最后通过临床神经化骨移植标本明确Sema3A与BMMSC活力的相关性及WNT通路的作用。这将为临床上通过神经调控干细胞活力，进而提高骨重建水平提供实验依据。

There is no effective preventive method for postoperative osteoporosis of bony grafts in jaw bone reconstruction. Our previous studies have demonstrated that innervation could regulate the mobilization and differentiation of bone marrow mesenchymal stem cells (BMMSCs) through neuro-transmitters therefore maintaining bone homeostasis. Based on these findings, we further developed a new method of innervated bone flaps which could markedly prevent osteoporosis of bony grafts in clinical practice. Semaphorin 3A (Sema3A) participates in neuro-modulation and affects bone remodeling, but the underlying stem cell-based mechanism remains obscure. Here we hypothesize that nerve-derived Sema3A could bind to Nrp1 expressed on BMMSCs, regulate genes such as nrp1 via WNT pathway, and then enhance BMMSC vitality in a positive feedback fashion. Using stem cell culture and DRG co-culture, animal models and clinical samples from innervated bone grafts, the present study will clarify the role of Sema3A in regulating BMMSC vitality and the possible positive feedback mechanism of Sema3A/Nrp1/WNT. We will further validate these mechanisms in vivo using a mouse model of mandibular denervation, Sema3A knockout mice and clinical samples from innervated bone grafts. We believe our study will provide a novel insight of the neural microenvironment-based stem cell mechanism in bone homeostasis, which is important to improve functional reconstructions for major defects in jaw bones.