骨质疏松症是危害健康的重大疾病，破骨细胞是参与骨质疏松的重要功能细胞，深入探索破骨细胞分化的调控机制，对发现骨质疏松治疗新靶点至关重要。课题组前期研究发现：Bre在破骨细胞分化过程中显著下调；敲除或沉默Bre可显著增强破骨细胞分化，而过表达Bre则抑制破骨细胞分化，但Bre对体内破骨细胞分化的调控作用及分子机制尚不清楚。本研究拟利用已构建完成的Bre基因敲除小鼠和转基因小鼠，运用骨形态计量学和组织学方法分析小鼠的骨吸收状态和骨量差异，以确定Bre对体内破骨细胞分化的调节作用。综合运用细胞与分子生物学研究方法，围绕Bre与破骨细胞分化抑制分子Hey1的结合，开展Bre调控破骨细胞分化的分子机制研究，并通过构建小鼠OVX骨质疏松模型探索Bre及Hey1在骨质疏松中的变化特征。以期明确Bre在破骨细胞分化和骨质疏松中的功能，从而为基于Bre靶点的药物设计提供实验基础和理论支撑。

Osteoporosis is a major health hazard and osteoclasts are important functional bone cells involved in the pathology of osteoporosis. Therefore, further exploration of the molecular mechanisms of osteoclast differentiation is essential for the discovery of novel therapeutic targets for osteoporosis. Our preliminary study found that the expression of Bre was significantly decreased during osteoclast differentiation. Knockout or knockdown of Bre expression significantly enhanced osteoclast differentiation, while overexpression of Bre inhibited osteoclast differentiation. However, the in vivo regulatory effect and molecular mechanism of Bre that affect osteoclast differentiation remained unclear. In the present study, we intend to use the method of bone morphometry and histology to investigate the difference in bone resorption and bone mass of Bre knockout mice and Bre transgenic mice and determine the in vivo regulative effect of Bre on osteoclast differentiation. Basis of the physically interacting between Bre and Hey1 and the inhibitory effect of Hey1 on osteoclast differentiation, we intend to combine methods in cell and molecular biology to investigate the molecular mechanism of Bre regulating osteoclast differentiation. Furthermore, changes of Bre and Hey1 in osteoporosis were studied by constructing mouse OVX osteoporosis model. The study intends to clarify the role of Bre in osteoclast differentiation and its involvement in osteoporosis and will provide an experimental basis and theoretical support for Bre-targeted drug design.