项目以lncRNA为视角，沿着ceRNA调控模式的思路，朝着系统阐述lncRNA TSC22D1-AS1/miR-765/BMP6轴向调控成骨分化过程的目标开展工作。研究由体内外两部分组成，体外以成人骨髓间充质干细胞成骨分化为对象，运用荧光素酶、荧光原位杂交和qPCR等技术鉴定相互间靶向关系，采取目标基因过表达（干扰）、靶基因回补等方法，分析成骨表型特征、成骨特异性基因表达和Smads蛋白磷酸化水平评价成骨能力；体内研究将不同表达水平lncRNA TSC22D1-AS1、miR-765和BMP6的hMSCs植入裸鼠皮下进行异位成骨，运用X线（钼靶）、HE染色、硬组织切片和体外相同的分子检测评估成骨效能。从体内外系统阐述lncRNA TSC22D1-AS1/miR-765/BMP6以轴向作用方式，经BMP6/Smads信号通路调控成骨分化的机制，为认识和治疗老年性骨质疏松提供新的思路和方法。

From the perspective of lncRNA, the project follows the idea of the ceRNA regulation mode and aims to systematically describe osteogenic differentiation of lncRNA TSC22D1-AS1/miR-765/BMP6 axial regulation. This study is divided into two parts (in vitro and vivo). It will be as a study object that human bone marrow mesenchymal stem cells differentiate into osteoblast in vitro. We will identify the relationship between each other by using luciferase, fluorescence in situ hybridization, and qPCR. Furtherly, overexpression (interference) of target genes and target gene replenishment experiments are carried to analyze the osteogenic phenotype, gene expression of osteogenic characteristics and Smads protein phosphorylation level in order to evaluate osteogenic ability. In vivo, hMSCs with different expression levels of lncRNA TSC22D1-AS1, miR-765 and BMP6 are implanted into nude mice subcutaneously for ectopic osteogenesis. Osteogenic potency is evaluated using X-ray (molybdenum target), HE staining, hard tissue slice and the same molecular assay with vitro. This study will systematically elaborate that lncRNA TSC22D1-AS1/miR-765/BMP6 (axial action) regulated the osteogenic differentiation mechanism via the BMP6/Smads signaling pathway in vitro and vivo. It will provide a new ideas and methods for profound understanding and treatment of senile osteoporosis.