Circ_HOMER1及其靶miRNAs调控人脐带间充质干细胞成骨分化的机制研究

人脐带间充质干细胞（hUCMSCs）是骨组织工程极具优势的种子细胞，但其成骨效果仍待提高，深入阐明其分化调控机制，可为提高其成骨效果并推动临床应用提供新策略。最新研究表明circRNA可通过其靶miRNAs调控细胞生长等生物学行为（Nat Commun，2016）。课题组前期联合circRNA、miRNA及表达谱芯片筛选出circ_HOMER1及其靶miRNAs，并初步证实circ_HOMER1可促进hUCMSCs成骨表型。故推测circ_HOMER1可通过其靶miRNAs调控hUCMSCs成骨分化。为验证此假说，本项目拟通过体外实验研究circ_HOMER1及其靶miRNAs对hUCMSCs成骨分化的影响及其调控机制；用裸大鼠体内实验进一步验证这一调控作用。预期研究结果有助于进一步阐明hUCMSCs成骨分化机制，提升其骨修复效果，并为circRNA调控干细胞分化提供理论与实践依据。

Human umbilical cord mesenchymal stem cells (hUCMSCs) are promising seed cells in bone tissue engineering, but their capability of bone formation still needs to be improved. Clarify their differentiation mechanism can help to improve their osteogenesis capability and clinical application. Circular RNA(circRNA) plays an important role in regulation of cell growth and other biological behaviors via its target microRNAs(miRNAs)( Nat Commun, 2016). Our group has combined with circRNA microarray, miRNA microarray and gene expression microarray to screen out circ_HOMER1 and its target miRNAs. And upregulation of circ_HOMER1 could make hUCMSCs possess osteogenic phenotype. In order to validate the hypothesis that the circ_HOMER1 could regulate the osteogenic differentiation of hUCMSCs via its target miRNAs, this project is preparing to explore the effects and mechanism of circ_HOMER1 and its target miRNAs on osteogenic differentiation of hUCMSCs in vitro; to further validate this regulatory mechanism in vivo in nude rats. The results will not only clarify the osteogenic differentiation mechanism of hUCMSCs and enhance their capability of bone regeneration, but also build on a solid theoretical and applied foundation for differentiation regulation of stem cells by circRNA.