骨细胞是骨骼中数量最多的细胞，在骨骼稳态维持发挥重要作用。我们前期研究发现FGFR1在骨细胞中敲除后，小鼠骨量增加，骨皮质增厚，提示FGFR1参与了对骨细胞的调控，但机制不清。Wnt/β-catenin是调节骨细胞功能的关键信号通路，在骨细胞中持续活化后也使骨量增加。进一步研究发现,骨细胞中敲除FGFR1后，Wnt/β-catenin信号增强，其抑制分子SOST表达明显下调。据此，我们提出骨细胞中FGFR1可能通过抑制Wnt/β-catenin信号来调控骨细胞功能，继而影响骨稳态，但机制不清。本课题拟建立在骨细胞中双敲除FGFR1与β-catenin的小鼠模型，通过对比观察突变小鼠和野生小鼠间骨骼表型差异，结合体外细胞和分子生物学实验，明确FGFR1是否通过β-catenin信号调控了骨细胞，并探讨相关机制。课题将首次明确FGFRs在骨细胞中的作用并揭示调控β-catenin可能的新机制。

Osteocyte is the most cells in bone, which play important roles in bone homeostasis.We found that deletion of FGFR1 in osteocyte led to increased bone mass,and increased cortical bonethickness, which indicated that FGFR1 participated in the regulation on osteocyte. Wnt/β-catenin signaling is the critical signaling regulating osteocyte. Continuing activating of β-catenin in osteocytes also led to increased bone mass and thicker cortical bone. Our studies further showed that deletion of FGFR1 in osteocyte led to increased β-catenin level and decreased Sclerostin(SOST), a critical inhibitor of Wnt/β-catenin signaling. These results suggested that FGFR1 may inhibit Wnt/β-catenin signaling. However, the mechanism is not clear. In this study, we first generate mouse models with double deletion of FGFR1 and β-catenin in osteocyte. Then we plan to analyze the bone phenotype of these mice and use cell culture experiments to study the mechanism of the regulation of FGFR1 on β-catenin. Our study will provide a new view to the role of FGFRs in osteocyte and the relationship with β-catenin.