TRPV6具有抑制破骨细胞形成和骨吸收功能的作用，但其确切机制仍不清楚。前期预实验发现：沉默TRPV6明显上调破骨细胞IGF信号通路上关键蛋白IGF1R和IGFBP1的表达；阻断IGF1R活性明显抑制TRPV6沉默诱导的破骨细胞分化能力。推测:TRPV6通过抑制IGF信号通路调控破骨细胞形成及骨吸收功能。因此，本项目拟在细胞和分子水平上，首先探讨TRPV6对破骨细胞增殖、分化、融合、凋亡和骨吸收的影响；其次研究IGF1R在TRPV6调控破骨细胞形成和骨吸收中的作用；然后研究TRPV6对破骨细胞IGF1R和IGFBPs表达的调控；最后研究TRPV6对破骨细胞IGF信号通路上的PI3K-AKT及MAPK-ERK途径的抑制作用。籍此揭示IGF信号通路介导TRPV6负向调控破骨细胞形成和骨吸收的作用及可能机制。研究结果将有助于完善骨质疏松的发病机制，并有望为临床治疗提供新的策略。

TRPV6 channel can suppress osteoclastic formation and bone resoption. However, the precise mechanisms remained elusive. Our pilot research data showed silence of TRPV6 gene can significantly increase the expression of two key protein of IGF signaling pathway in osteoclast, IGF1R and IGFBP1. Blocking IGF1R can suppress the increasing osteoclastic differentiation induced by silence of TRPV6 gene. On the basis of this information, we presume that TRPV6 represses the IGF signaling pathway to suppress osteoclast formation and bone resorption. In order to explain this hypothesis, both cell and molecular research will be done. Firstly, the role of TRPV6 on osteoclastic differentiation, cell-cell fusion, survival and bone resorption will be confirmed. Secondly, IGF1R mediated-TRPV6 regulating osteoclast formation and bone resorption will be done. Thirdly, the regulation of TRPV6 on the expression of IGF1R and IGFBP in osteoclast will be clarificated. Finally, IGF-induced PI3K-AKT and MAPK-ERK signaling pathway suppressed by TRPV6 will be revealed. According to this study, the molecular mechanisms underlying the negative regulation of TRPV6 on osteoclast formation and bone resorption through IGF signaling pathway will be found.As a result, the pathogenesis of osteoporosis will be supported by new scientific evidences. A potential therapeutic target may be found to treat the osteoporosis in the future.