YAP1 influences differentiation of osteoblastic MC3T3-E1 cells through the regulation of ID1
YAP1 influences differentiation of osteoblastic MC3T3-E1 cells through the regulation of ID1
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YAP1通过调节ID1影响成骨细胞MC3T3-E1细胞的分化
DOI：
10.1002/jcp.28088
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发表时间：
2019
影响因子：
5.6
通讯作者：
Wang Jiawei
中科院分区：
文献类型：
--
作者：
Yang Beining;Sun Hualing;Chen Peiyu;Fan Nana;Zhong Heli;Liu Xiayi;Wu Yanru;Wang Jiawei
是相关蛋白1（YAP 1）转录辅激活因子最近被确定为调节骨骼谱系细胞分化和骨发育。然而，YAP 1在成骨细胞分化调控中的作用和分子机制仍有待阐明。在这项研究中，我们证明了在大鼠骨髓间充质干细胞和MC 3 T3-E1的成骨分化过程中，YAP 1的表达增加。YAP 1过表达的MC 3 T3-E1显示成骨标志物的表达增加，如侏儒相关转录因子2、骨钙素和骨桥蛋白，以及碱性磷酸酶和茜素红染色。相反，YAP 1敲低显著抑制MC 3 T3-E1成骨细胞分化。从机制上讲，我们发现YAP 1过表达上调了分化抑制因子/DNA结合1（ID 1）的mRNA和蛋白表达，这与YAP 1敲低组的结果相反。此外，ID 1过表达增强了MC 3 T3-E1细胞的早期成骨分化。此外，用外源性ID 1过表达质粒瞬时转染完全恢复了YAP 1敲低对MC 3 T3-E1细胞分化的降低作用。此外，β-catenin和AMP激活的蛋白激酶信号通路参与了YAP 1的调控过程。综上所述，我们的研究表明，YAP 1是体外成骨细胞分化的重要调节因子，并为深入了解YAP 1调节成骨细胞分化的机制提供了依据。
Yes‐associated protein 1 (YAP1) transcriptional coactivator has recently been identified to regulate skeletal lineage cell differentiation and bone development. However, the role and molecular mechanisms of YAP1 in the regulation of osteoblastic differentiation remains to be elucidated. In this study, we demonstrated that YAP1 expression was increased during osteogenic differentiation of rat bone mesenchymal stem cells and MC3T3‐E1. YAP1 overexpression MC3T3‐E1 showed increased expression of osteogenesis markers, such as runt‐related transcription factor 2, osteocalcin, and osteopontin, as well as alkaline phosphatase and alizarin red staining. Conversely, YAP1 knockdown significantly suppressed MC3T3‐E1 osteoblastic differentiation. Mechanistically, we found that YAP1 overexpression upregulated the mRNA and protein expression of the inhibitor of differentiation/DNA binding 1 (ID1), which was contrary to the results of YAP1‐knockdown group. Moreover, the early osteogenic differentiation of MC3T3‐E1 cells was enhanced by ID1 overexpression. Furthermore, transient transfection with exogenous ID1 overexpression plasmid completely recaptured the decreased effects of YAP1 knockdown on MC3T3‐E1 cell differentiation. In addition, β‐catenin and AMP‐activated protein kinase signaling pathways participated in YAP1 regulation processes. Taken together, our study suggests that YAP1 is a crucial modulator of osteoblast differentiation in vitro, and provides insight into the mechanism by which YAP1 regulates osteoblast differentiation.