Micro-26a协同调节PTEN/AKT与BMP/SMAD信号通路促进大面积骨缺损修复的机制研究

项目名称： Micro-26a协同调节PTEN/AKT与BMP/SMAD信号通路促进大面积骨缺损修复的机制研究

项目编号： No.31501036

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 李岩

作者单位： 中国人民解放军第四军医大学

项目金额： 20万元

中文摘要： 骨再生是由成血管与成骨信号通路之间组成的交叉网络共同调控的。因此，愈合早期促进血管形成是提高骨修复能力的关键。前期研究发现:miR-26a能够有效的同时促进愈合早期微血管形成与骨组织的再生，最终理想的促进大面积骨缺损修复。通过生物信息学分析并结合实验研究结果，我们近期发现与成血管（PTEN/AKT）及成骨（BMP/SMAD）关键信号通路密切相关的基因PTEN、DUSP4、 GSK-3β、TOB1、SMAD4 可能皆为miR-26a的靶基因。因此，miR-26a可能通过协同调节PTEN/AKT与BMP/SMAD而有效的促进了大面积骨修复，但其具体的作用机制有待进一步阐明。本项目将从分子、细胞、动物模型三个层次探明miR-26a协同调节PTEN/AKT与BMP/SMAD信号通路的分子机制，建立成血管－microRNA－成骨调节环路，为骨缺损修复的调控机制提供新的思路。

中文关键词： 动物；非编码RNA；靶基因；调控网络；生物信息学预测

英文摘要： Bone regeneration was regulated through the crossover network with the interactions between angiogenic and osteogenic signaling pathways. Therefore, enhancing vascularization in initial stage after implantation is very important to enhance bone repair ability. Our previous study found that miR-26a could simultaneously enhance angiogenesis and osteogenesis and therefore effectively enhance microvessel formation in initial stage, which resulted in critical size calvarial bone defect completely repair. Based on in silica analysis and the recent results, we found that the genes including PTEN, DUSP4, GSK-3β, TOB1 and SMAD4 involved in key angiogenic-osteogenic (PTEN/AKT-BMP/SMAD) signaling pathways may be all targets genes of miR-26a. It could be hypothesized that miR-26a may couple PTEN/AKT and BMP/SMAD signaling pathways to enhance bone regeneration. However, the mechanism underlying miR-26a regulating is still unclear. Therefore, this study is to elucidate molecular mechanism underlying miR-26a coupling angiogenic－osteogenic (PTEN/AKT－BMP/SMAD) signaling pathways to enhance bone regeneration based on the molecular, cell and animal model, and further construct the regulatory loop among angiogenesis-miRNA-osteogensis. Our study may reveal a novel mechanism whereby miR-26a played a critical role in bone regeneration, which has important theoretical and clinic significance.

英文关键词： animal;non-coding RNA;target gene;regulatory network;in silica analysis