Analysis of regulation of osteogenesis by Notch signaling andits application to boneregeneration therapy

Notch信号传导对于组织和细胞分化的多个方面是必需的。在这项研究中，我们确定了锌指蛋白64（Zfp64）作为一种新的Notch 1的共激活因子。Zfp 64与Notch 1的胞内结构域相关，被募集到Notch靶基因Hes 1和Hey 1的启动子，并反式激活这些Notch下游基因。Zfp64的表达受Runx2的控制，并且通过其启动子的直接反式激活而上调。Zfp 64抑制C2C12细胞的肌源性分化并促进其成骨分化。我们的数据证明了Zfp64的两个功能方面：它是Runx2的下游靶点，其同源蛋白作为Notch 1的共激活因子，表明Zfp64通过调节Notch信号传导介导间充质细胞分化。

Notch signaling is required for multiple aspects of tissue and cell differentiation. In this study, we identified zinc finger protein 64 (Zfp64) as a novel coactivator of Notch1. Zfp64 is associated with the intracellular domain of Notch1, is recruited to the promoters of the Notch target genes Hes1 and Hey1, and transactivates these Notch downstream genes. Zfp64 expression is under the control of Runx2, and is upregulated by the direct transactivation of its promoter. Zfp64 suppresses the myogenic differentiation of C2C12 cells and promotes their osteoblastic differentiation. Our data demonstrate two functional aspects of Zfp64: it is a downstream target of Runx2 and its cognate protein acts as a coactivator of Notch1, suggesting that Zfp64 mediates mesenchymal cell differentiation by modulating Notch signaling.