瓣膜间质细胞成骨分化是主动脉瓣钙化发生的核心过程，其调控机制是心脏瓣膜病领域的前沿科学问题。我们的前期研究显示：胚胎发育过程中调控细胞分化的关键转录因子Oct4在钙化瓣膜组织中的表达被重启，其在瓣膜间质细胞中的表达增高能上调Cripto-1表达，并引起瓣膜间质细胞向成骨细胞分化。此外，Cripto-1在钙化瓣膜中表达也显著增高。相关文献表明，Cripto-1是参与活化Wnt/β-Catenin信号通路的重要膜蛋白，而后者恰是介导瓣膜间质细胞成骨分化的关键通路。据此，本课题拟研究瓣膜间质细胞中Oct4上调Cripto-1表达的转录调控机制，并在细胞及动物模型水平研究Oct4/Cripto-1/Wnt/β-Catenin调控轴介导瓣膜间质细胞成骨分化在主动脉瓣钙化发生中的作用，为主动脉瓣钙化的防治提供新的靶点。

The osteoblast differentiation of valve interstitial cells (VICs) is the core process of aortic valve calcification. The regulatory mechanism of this process is a frontier scientific problem in the field of heart valve disease. Our previous study show that: Oct4, the key transcriptional factor regulating cell differentiation during embryonic development, is restarted in the calcified valve tissue. The increased expression of Oct4 in VICs lead to the upregulation of Cripto-1 expression and cause the cells differentiate into osteoblasts. In addition, the expression of Cripto-1 is also significantly upregulated in the calcified valve. Related literatures show that Cripto-1 is an important membrane protein involved in the activation of Wnt/β-Catenin signaling pathway, which is precisely the key pathway regulating the osteoblast differentiation of VICs. Accordingly, this study propose to explore the transcriptional regulation mechanism of Oct4 on Cripto-1 in VICs, investigate the effect of Oct4/Cripto-1/Wnt/β-Catenin regulating axes on the osteoblast differentiation of VICs during the development of aortic valve calcification, and thus provide novel target for the prevention and treatment of calcified aortic valve disease.