招募足够数量的MSCs至骨折端对骨折修复至关重要。多种非编码RNA参与干细胞迁移，然其作用靶点和机制不详。我们前期工作发现补肾活血汤促进lncRNA PVT1表达，诱导MSCs迁移，加快骨折愈合。但PVT1在MSCs迁移中的作用以及补肾活血汤如何激活PVT1、诱导趋化因子表达、促进骨折修复的分子机制仍需深入探讨。故本项目拟运用流式细胞、ELISA、qRT-PCR、Western blot、细胞趋化实验、双荧光素酶报告基因、RIP、RNA Pull-down、CHIP、免疫组化等技术手段，借助临床病人标本、细胞、动物骨折模型，从表观遗传修饰、转录后水平研究PVT1如何通过miR-503-5p诱导趋化因子表达，促进MSCs迁移以及补肾活血汤的调控机制。本项目提出以lncRNA→miRNA→mRNA为主的MSCs迁移调控模式，为中医补肾活血法促进老年骨折修复的分子机制研究提供全新思路和理论依据。

It is very vital for fracture repair to recruit adequate mesenchymal stem cells to fracture area. There are various noncoding RNAs involved in migration of stem cells. However, those concrete targets and mechanisms are unknown. Our previous work found that BuShenHuoXueTang can enlarge the expression of long noncoding RNA PVT1, induce migration of MSCs and accelerate fracture healing. But the effect of PVT1 in migration of MSCs and the molecular mechanism of BuShenHuoXueTang how to activate long noncoding RNA PVT1, induce chemokine expression and accelerate fracture repair need to be deeply investigated. So, the approaches, for example, flow cytometry, ELISA, qRT-PCR, western blot, cell chemotactic experiment, dual luciferase reporter, RIP, RNA Pull-down, CHIP and immunohistochemical analysis will be used in the project. By aid of the clinic patient`s samples, cell, and animal fracture model, we will investigate PVT1 how to induce chemokine expression, promote migration of MSCs through miR-503-5p from epigenetic modification and post-transcriptional level and regulatory mechanism of BuShenHuoXueTang. Taken together, It will offer not only a novel regulation mode for migration of MSCs mainly on lncRNA→ miRNA→ mRNA, but also a new research idea and theoretical basis of the molecular mechanism study for TCM therapy of BuShen and HuoXue in fracture repair of elderly people.