miR-145通过抑制Semaphorin3A调节成骨细胞分化的机制研究

miR-145 is a differentially expressed miRNA in the jaw bone marrow mesenchymal stem cells (JBMMSC) screened by chip technology. miR-145 is highly expressed in JBMMSC. However, its roles in JBMMSC differentiation is not known now. Our preliminary data showed that inhibition of miR-145 could significantly promote the differentiation of JBMMSC to osteoblasts. In addition, bioinformatics analysis showed that Semaphorin3A was the target gene of miR-145. Semaphorin3A expression was significantly up-regulated by miR-145 silence in the JBMMSC. Therefore, miR-145 may regulate the differentiation of JBMMSC to osteoblast by inhibition of Semaphorin3A gene expression. This study will clarify the biological features of miR-145, evaluate the effects of miR-145 on the differentiation of JBMMSC and Semaphorin3A expression using overexpression / silence strategy, explore the mechanisms by which miR-145 regulates JBMMSC differentiation. The roles and mechanisms of miR-145 in the differentiation of JBMMSC are not reported till now. Results of this study will provide a new therapeutic targets potential for the prevention and treatment of bone defect and osteoporosis.

miR-145是我们采用芯片技术筛选到的、差异高表达于颌骨骨髓间充质干细胞（JBMMSC）中、功能未知的miRNA。前期研究发现抑制miR-145明显促进JBMMSC向成骨细胞分化；生物信息学分析发现Semaphorin3A（Sema3A）为其靶基因；而Sema3A的表达在miR-145沉默的JBMMSC中显著上调，提示miR-145可能通过抑制Sema3A基因的表达而调节JBMMSC向成骨细胞的分化。本研究拟：阐明miR-145的生物学特征；以基因过表达/沉默策略，评价miR-145对JBMMSC的成骨分化及Sema3A表达的影响；以Sema3A为机制研究切入点，通过过表达/沉默Sema3A基因，系统论证miR-145影响JBMMSC分化的分子机制。miR-145在JBMMSC分化中的功能、与分化之间的关系及机制未见报道，本研究可为骨缺损及骨质疏松的防治提供新的靶点。

miR-145是我们采用芯片技术筛选到的、差异高表达于颌骨骨髓间充质干细胞（JBMMSC）中、功能未知的miRNA。前期研究发现抑制miR-145明显促进JBMMSC向成骨细胞分化；生物信息学分析发现Semaphorin3A（Sema3A）为其靶基因；而Sema3A的表达在miR-145沉默的JBMMSC中显著上调，提示miR-145可能通过抑制Sema3A基因的表达而调节JBMMSC向成骨细胞的分化。本研究通过基因过表达/沉默策略，阐明miR-145的生物学特征，评价miR-145对JBMMSC的成骨分化及Sema3A表达的影响；以Sema3A为机制研究切入点，通过过表达/沉默Sema3A基因，系统论证miR-145影响JBMMSC分化的分子机制。结果表明：miR-145抑制人颌骨骨髓间充质干细胞（h-JBMMSCs）成骨分化；Sema 3A是miR-145直接靶基因；miR-145通过靶向调节Sema 3A的表达而抑制成骨分化。本研究可为骨缺损及骨质疏松的防治提供新的靶点。