流体剪切应力通过TGFBR2/ERK5信号通路调控成骨细胞和破骨细胞的生理功能：基于竞争性内源RNA/ceRNA的分子机制研究

应力环境在抗骨质疏松发生中具有重要作用，我们已证实流体剪切力（FSS）和ERK5信号通路在促进骨形成过程中发挥关键作用，但竞争性内源RNA（ceRNA）在其中的作用仍不清楚。前期测序结果及相关实验显示FSS分别通过circRNA CDR1as和LncRNA XIST两种ceRNA调节成骨细胞和破骨前体细胞的生物学功能，生物信息学分析显示CDR1as、XIST和TGFBR2均具有miR-7结合位点。因此我们认为加载FSS后CDR1as和XIST分别竞争性结合成骨细胞和破骨细胞内miR-7，进而靶向调节TGFBR2/ERK5通路，促进成骨细胞增殖和抑制破骨前体细胞分化，防止骨质疏松的发生发展。本项目拟从细胞、分子和整体水平探索CDR1as/XIST-miR-7-TGFBR2-ERK5信号轴在FSS调控成骨细胞增殖和破骨前体细胞分化过程中的作用，为骨质疏松症的防治提供新的治疗靶标。

The stress environment plays an important role in resisting osteoporosis. We have demonstrated that fluid shear stress (FSS) and the ERK5 signaling pathway play key roles in promoting bone formation. But the role of competing endogenous RNA (ceRNA) remain unclear. Previous sequencing results and related experiments show that FSS regulates the biological functions of osteoblasts and osteoclast precursor cells by circRNA CDR1as and LncRNA XIST respectively, which is a pair of ceRNA. Besides, bioinformatic analysis shows that CDR1as, XIST and TGFBR2 have a common miR-7 binding site. Therefore, we believe that after loading FSS, CDR1as and XIST competitively bind to miR-7 in osteoblast and osteoclast precursor cell respectively, and then promote osteoblast proliferation and inhibit osteoclast precursor cell differentiation by targeting regulate the TGFBR2/ERK5 pathway, finally preventing the occurrence and development of osteoporosis. This program aims to explore the role of CDR1as/XIST-miR-7-TGFBR2-ERK5 signal axis in the regulation of osteoblast proliferation and osteoclast precursor cell differentiation by FSS from the cellular, molecular and overall levels, thus providing new therapeutic targets for the prevention and treatment of osteoporosis.