老年骨质疏松患者骨髓间充质干细胞中lncRNA/miRNA表达变化和调控机制尚不清楚。我们的前期研究结果证实，与正常人骨髓间充质干细胞（BMMSCs）相比，lncRNA SEMA3B在骨质疏松患者中表达降低，但在成骨分化过程中逐渐增加。SEMA3B可以潜在靶定miR-214并抑制其表达，miR-214下游具有多个骨分化相关靶基因ATF4、 FGFR1、 PTEN、Osterix。我们推测SEMA3B通过直接调控miR-214影响靶基因表达，从而调控干细胞成骨分化。.本课题拟应用pull-down、双荧光素酶报告系统等手段探索BMMSCs中SEMA3B/miR-214及靶基因对成骨分化的影响及调控机制，研究SEMA3B在快速老化模型小鼠中的治疗效果及机制，最终阐明SEMA3B/miR-214/靶基因介导的分子通路在骨质疏松发生发展中的机制，为更好的治疗骨质疏松疾病提供新的理论依据和治疗靶点。

The expression profile and regulation mechanism of lncRNAs/miRNAs in the senile osteoporosis bone marrow mesenchymal stem cells (BMMSCs) remains unclear. Our previous results confirmed that compared with the BMMSCs in normal subjects, the expression of lncRNA SEMA3B was decreased in the senile patients with osteoporosis, while was increased in the process of osteogenic differentiation. SEMA3B can potentially target miR-214 and inhibit its expression. Four bone differentiation related genes, including ATF4, FGFR1, PTEN, Osterix, were predicted targets of miR-214. We speculated that SEMA3B may affect the expression of downstream target genes by directly targeting miR-214 , therefore, regulating the osteogenic differentiation of BMMSCs. .Using pull-down, dual luciferase reporter system, we aimed to explore the effects of SEMA3B/miR-214 and its target genes on osteogenic differentiation of BMMSCs and its regulation mechanism. The therapeutic effect and mechanism of SEMA3B in the rapid aging model mice SAMP6 will be further conducted. These studies may finally clarify the molecular regulatory pathway of SEMA3B/miR-214/target genes in the development of osteoporosis and provide a new theoretical basis and therapeutic targets for better treatment of osteoporosis disease.