动脉钙化是血管壁发生的一种类似骨形成的主动调节过程，严重危害患者健康。血管平滑肌细胞（VSMCs）向成骨细胞分化是动脉钙化的细胞学基础。我们的前期研究发现Ghrelin可通过GHSR-1α/ERK途径抑制VSMCs向成骨细胞分化，同时Ghrelin调节钙化型血管平滑肌细胞（CVSMCs）的OPG/RANKL表达。本项目探讨Ghrelin调控VSMCs OPG/RANKL表达的转录调节机制和细胞信号转导通路；采用shRNA-OPG和腺病毒-Ghrelin分别低表达和过表达OPG和RANKL，阐明OPG/RANKL在Ghrelin缓解VSMCs向成骨细胞分化的分子机制。通过在动脉钙化动物模型，构建Ghrelin过表达/OPG基因敲除小鼠，观察Ghrelin在体内对动脉钙化的影响及其机制。本项目在原有研究的基础上，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。

Arterial calcification is a positive regulation process resembling bone formation in arterial wall, which can induce serious consequence and threaten the patient's health. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is the cytologic mechanism of arterial calicification. Our previous studies demonstrate Ghrelin attenuates osteoblastic differentiation of VSMCs through GHSR-1α/ERK pathway. Meanwhile, Ghrelin regulates the expression of OPG/RANKL in calcifying vascular smooth muscle cells (CVSMCs). To clarify the transcirption mechanism and signaling pathway invovled in Ghrelin regulating OPG/RANKL expression, luciferase reporter assay and cell signaling inhibitor will be used in beta-glycerophosphate induced VSMCs and CVSMCs. To explore whether OPG/RANKL involved in Ghrelin reducing osteoblastic differentiation of VSMCs, shRNA-OPG and adenovirus-Ghrelin will be used. To investigate the effect of Ghrelin on arterial calcifcation in OPG gene knockout mouse, a Ghrelin overexpression will be constructed using adviurs vector. The project devote to reveal the new mechanism of arterial calcification and find the new target for treatment of arterial calcificaiton.