Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts
Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts
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DOI：
10.1002/1873-3468.14016
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发表时间：
2020-12
期刊：
影响因子：
3.5
通讯作者：
Chang-Hwan Seong;N. Chiba;Joji Kusuyama;M. S. Amir;Nahoko Eiraku;Sachiko Yamashita;T. Ohnishi;N. Nakamura;T. Matsuguchi
中科院分区：
文献类型：
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作者：
Chang-Hwan Seong;N. Chiba;Joji Kusuyama;M. S. Amir;Nahoko Eiraku;Sachiko Yamashita;T. Ohnishi;N. Nakamura;T. Matsuguchi
骨形态发生蛋白（Bone morphogenetic protein， BMP） 9是最具成骨性的BMP之一，但其作用机制尚未完全阐明。Hes1是一个具有基本螺旋-环-螺旋结构域的转录调节因子，是Notch信号传导的一个众所周知的效应因子。在这里，我们发现BMP9诱导成骨细胞Hes1 mRNA和蛋白表达的周期性增加，可能是通过自分泌负反馈机制。BMP9介导的Hes1诱导被ALK抑制剂和Smad7（一种抑制性Smad）的过表达显著抑制。荧光素酶和ChIP分析显示，小鼠Hes1基因5 '上游区域的两个Smad‐结合位点对于BMP9的转录激活至关重要。因此，我们的数据表明BMP9通过Smad信号通路诱导Hes1在成骨细胞中的表达。
Bone morphogenetic protein (BMP) 9 is one of the most osteogenic BMPs, but its mechanism of action has not been fully elucidated. Hes1, a transcriptional regulator with a basic helix‐loop‐helix domain, is a well‐known effector of Notch signaling. Here, we find that BMP9 induces periodic increases of Hes1 mRNA and protein expression in osteoblasts, presumably through an autocrine negative feedback mechanism. BMP9‐mediated Hes1 induction is significantly inhibited by an ALK inhibitor and overexpression of Smad7, an inhibitory Smad. Luciferase and ChIP assays revealed that two Smad‐binding sites in the 5′ upstream region of the mouse Hes1 gene are essential for transcriptional activation by BMP9. Thus, our data indicate that BMP9 induces Hes1 expression in osteoblasts via the Smad signaling pathway.