组蛋白去甲基化蛋白PHF8调控Satb2在失重性骨质疏松中的作用及机制研究

失重性骨质疏松呈持续性进展且防护效果有限，已成为载人航天中亟需解决的重大问题之一，其发病机制为骨形成减少而非骨吸收增强，近期发现，失重可致骨髓间充质干细胞（BMSC ）增殖和分化功能异常，进而影响机体骨形成。BMSC向成骨分化受多种基因和蛋白调控，已证实，模拟失重可引起BMSC转录因子Satb2表达下降，从而引起Runx2表达降低，进而导致BMSC分化受阻。而组蛋白去甲基化蛋白PHF8能够结合到Satb2的启动子区域激活Satb2基因的表达，促进成骨细胞分化。本研究利用回转器和大鼠尾吊法建立细胞和动物水平模拟失重效应，在前期研究基础上，以模拟失重后BMSC功能异常为切入点，重点分析PHF8-Satb2在失重性骨质疏松中的作用及机制，继而对PHF8的功能活性和表达进行人工干预，发现控制该途径的关键分子，该研究可为失重性骨质疏松的分子机制作出新的补充，为预防骨质疏松的新药物靶点筛选提供新思路。

Because the significant osteoporosis induced by weightlessness has no self-limitation and lack of effective countermeasures, it has become one of the most medical problems during long-term spaceflight. It has been reported that the decrease in osteoblast function and bone formation resulted in weightlessness-induced osteoporosis. Resent studies showed that changes of bone marrow mesenchyme stem cells (BMSCs) were also involved in this process and thePHF8 regulated stab2 plays important role in bone formation. However, the cellular and molecular mechanism underlying it remain to be fully elucidated. Based on our previous results, in this study, we introduce the hind limb unloading rats and clinorotation-induced cell as simulated weightlessness models to explorer the changes of BMSCs after weightlessness. The alterations of PHF8 and Satb2expressionin BMSCs were to be explored to investigate the mechanisms of osteoporosis induced by weightlessness. In order to further clarify the key molecule in regulating this process, we examine the changes of BMSCs function by interfering the activities ofPHF8 and Stab2. Our study will provide experiment data for the mechanism of osteoporosis induced by weightlessness. Our finding might help to know the possible mechanism of the BMSCs and OB function alteration and provide some theoretical basis to the protection of osteoporosis induced by weightlessness.