前期工作发现成纤维生长因子受体3（FGFR3）可通过直接促进破骨细胞分化和骨吸收功能及影响成骨细胞中RANKL/OPG来间接促进破骨细胞形成。雌激素受体α（ER-α）通路发挥相反作用，负性破骨细胞分化和功能。FGFRs的下游的MAPK与PI3K/AKT可参与对ER-α活性的调控，我们前期研究也发现FGFR3可降低ER-α蛋白水平，呈剂量依赖性，并且与FGFR3的激活程度相关。根据上述发现和文献，我们推测FGFR3可能通过抑制ERα活性或表达水平调节破骨细胞功能促进破骨细胞分化及骨吸收功能。我们将利用在破骨和成骨细胞中双敲除FGFR3并敲除ER-α的小鼠模型，结合体外小鼠原代成骨细胞/破骨细胞培养，及相关细胞系实验，观察FGFR3与ER-α间交互作用对小鼠破骨细胞形成和功能的影响，以及FGFR3调控ER-α的相关分子机制，为通过干预该信号网络调控破骨细胞功能，防治骨代谢性疾病提供实验基础。

FGFR3 can promote osteoclast differentiation and bone resorption directly or though increased RANKL/OPG produced by osteoblasts. ER-α negatively regulates osteoclast differentiation and resorption. MAPK and PI3K/AKT which is also the downstream pathway of FGFRs can regulate the activity of ER-α. We previously found that FGFR3 can downregulate the protein level of ER-α. So we presume that FGFR3 may promote osteoclast activity by inhibiting ER-α activity or expression. In this study, we plan to useFGFR3 and ER-α double knockout mice and the cell experiments to study the The effect of interaction between FGFR3 and ERɑ on osteoclast differentiation.