力学信号是启动牙槽骨改建最重要的生物信号之一，应力作用下骨髓基质干细胞（BMSCs）骨向分化的调控机理已成为正畸学和生物力学的交叉研究热点。本课题组前期研究证实Cbfa1在力传导中起关键作用，而其上游调控机制亟待阐明。由于新揭示的与早期骨向分化密切相关的的转录因子FoxO1与Cbfa1有较强的相关性，生物信息学也表明FoxO1可以与Cbfa1的启动子直接结合。因此，提出假设：FoxO1可能通过在转录水平调控Cbfa1的表达，即FoxO1-Cbfa1轴可能在应力调控BMSCs骨向分化中起重要作用。本项目拟通过荧光素酶报告系统及染色质免疫共沉淀鉴定FoxO1与Cbfa1启动子的直接结合，RNA干扰阻断或基因克隆上调FoxO1，激活或阻断上游通路，并进行体内实验。多层次研究应力刺激下BMSCs骨向分化的生物学行为，为通过调控该基因促进局部骨改建、缩短正畸疗程提供实验依据，开拓新的力学生物学思路。

The mechanism of mechanical signal trigger the biological signal to remodel the alveolar bone and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under mechanical stress is the focus of interdisciplinary studies in the fields of both orthodontics and biomechanics. The works of National Natural Science Foundation of China-Youth project has proven the vital role of Cbfa1 in mechanotransduction, however, the mechanism of its upstream regulation remains unclear. We screened some key proteins involving in bone modeling under the stress through the protein chip and gene chip technology, With a review of the literature and previous studies, we have proven the relationship between FoxO1 and Cbfa1, moreover, found the fact that FoxO1 combine the promoter of Cbfa1 directly in virtue of methods of bioinformatics. So, we hypothesize that FoxO1 might regulate the expression of Cbfa1 at the level of transcription, the axis of FoxO1- Cbfa1 might, as a key factor, regulate the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under mechanical stress through three pertinent upstream pathways. This present project will identify that FoxO1 could combine the promoter of Cbfa1 directly by Luciferase reporter system and Chromatin immunoprecipitation and the silence and increase of FoxO1 with by means of RNAi and gene cloning techniques, furthermore, we will prove this hypothesis in vivo. Altogether, we intend to study the biological behaviour of osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under stress by regulating the axis of FoxO1- Cbfa1, which will exploit the new area in promoting the local alveolar bone remodeling.