失重性骨质疏松由于没有自限性且防护效果不佳，已成为航天医学中迫切需要解决的重大问题之一，目前认为其发病机制主要是成骨细胞增殖分化障碍及骨形成减少。近期研究认为，失重后骨髓间充质干细胞分化障碍不容忽视，而转录因子stab2成骨分化中发挥重要作用。本研究利用独特的细胞回转器模拟失重效应，并建立尾吊大鼠的模拟失重模型，采用多种分子生物学技术，在前期研究工作的基础上，揭示骨髓间充质干细胞和成骨细胞在失重导致骨丢失中的作用，通过对模拟失重致骨髓间充质干细胞和成骨细胞功能异常的分子机制研究，明确转录因子Satb2/Hoxa2/Runx2参与失重后骨质疏松信号传导的方式，继而对Satb2和Hoxa2的功能活性和表达进行人工干预，发现控制该途径的关键信号转导分子，从而对失重性骨质疏松的机制探讨作出新的补充，为确定能否成为延缓或阻止失重性骨质疏松的药物设计靶点提供新的思路和理论依据。

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 (OB) 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 the transcriptional factor 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 hindlimb unloading rats and clinorotation-induced cell as simulated weightlessness models to explorer the changes of BMSCs and OB function after weightlessness. The alterations of Satb2/Hoxa2/Runx2 expression in BMSCs and OB 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 and OB function by interfering the activities of Stab2 and Hoxa2. 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.