调控间充质干细胞（MSCs）向成骨细胞分化是骨质疏松症的研究热点之一。SOST是骨形成重要信号通路--Wnt通路的重要抑制因子。项目组运用lncRNA芯片分析首次发现lncRNA-AF289591在骨质疏松人群中高表达；抑制AF289591可促进MSCs向成骨细胞分化，SOST是AF289591的靶基因。前期研究显示SOST表达受锌指蛋白(Zfp)467调控。预实验表明AF289591可促进Zfp467表达并增强Zfp467与SOST相互作用。在此基础上，本课题拟在分子、细胞及动物实验水平上对AF289591与SOST间的相互关系，AF289591对SOST的调控机制以及AF289591是否通过SOST调控Wnt通路从而影响骨形成的分子机制进行深入研究，旨在阐明AF289591与骨质疏松症的相关性及其在调控成骨分化中的作用，为骨质疏松症的治疗提供新思路和理论依据。

The osteogenic differentiation regulation of mesenchymal stem cells (MSCs) is one of the research hotspots in osteoporosis. SOST is an important inhibitor of Wnt signal pathway, which is key signal pathway for bone formation. Our previous studies first demonstrated that the expression of lncRNA-AF289591 was upregulated in osteoporosis patients through lncRNA microarray assay; inhibition of AF289591 promoted osteogenic differentiation and reduced the expression of SOST. The expression of SOST was regulated by Zinc finger protein 467( zfp467). In our current study, we found that AF289591 blocked the Wnt signaling by enhancing the expression of Zpf467 and interaction of Zpf467 and SOST. Base on these data, we will further investigate the role and mechanism of AF289591 on the modulation of Wnt signaling to verfy that the interaction between AF289591 and SOST; The regulation mechanisms AF289591 on SOST ；and AF289591 regulate Wnt signaling via modulating the expression of SOST, which will provide new potential therapeutic target for osteoporosis.rosis.