血管平滑肌细胞（VSMCs）向成骨细胞（OB）分化是动脉钙化的重要原因，Genistein可抑制VSMCs分化，但其分子机制并不明确。我们前期研究提示：Genistein可调节VSMCs中OPG表达， OLCs可调控OB分化。据此，我们推测Genistein通过OPG/RANKL系统不仅直接抑制VSMCs向OB分化，而且通过调控OLCs功能，减少IGF-1和TGF-β表达来抑制VSMC分化。本项目拟采用病毒载体在VSMCs中降低和过表达OPG基因，阐明OPG/RANKL是Genistein调控VSMCs向OB分化的中介分子；将OLCs与VSMCs共培养，探讨OLCs调控VSMCs向OB分化的分子机制。构建OPG基因过表达/敲除小鼠，建立动脉钙化动物模型，研究Genistein在体内对动脉钙化的影响及其具体机制。本项目旨在揭示动脉钙化新的发病机制，为动脉钙化防治提供新的作用靶点和理论依据。

Vascular smooth muscle cells (VSMCs) differentiation into osteoblasts (OB) is an important cause of arterial calcification. Genistein inhibits VSMCs differentiation, but its molecular mechanism is unclear. We found that: (1) Genistein regulates OPG expression of VSMCs, (2) Osteoclast-like cells (OLCs) regulates OB differentiation. We propose that Genistein inhibits VSMCs to OB differentiation, inhibits OLCs functions and reduces IGF-1 and TGF-β expression through OPG / RANKL system. The project is to investigate that OPG/RANKL is the mediated molecular of Genistein regulates VSMCs to OB differentiation by siRNA-OPG and adenovirus-OPG；Then to explore the molecular mechanism of OLCs regulation of VSMCs to OB differentiation by culturing VSMCs and OLCs cells together. Finally to study the effect of Genistein on arterial calcification in vivo by building OPG gene overexpression/knockout mice and establishing arterial calcification animal model. This project will provide a new theoretical basis for revealing the pathogenesis and prevention of arterial calcification.