Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts,FEBS Letters

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Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts
FEBS Letters ( IF 3.0 ) Pub Date : 2020-12-25 , DOI: 10.1002/1873-3468.14016
Chang-Hwan Seong _{1,

2} , Norika Chiba ₂ , Joji Kusuyama _{2,

3,

4} , Muhammad Subhan Amir _{1,

2,

5} , Nahoko Eiraku ₆ , Sachiko Yamashita ₂ , Tomokazu Ohnishi ₂ , Norifumi Nakamura ₁ , Tetsuya Matsuguchi ₂

Affiliation

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 (bHLH) 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 chromatin immunoprecipitation 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.

中文翻译：

骨形态发生蛋白 9 (BMP9) 通过成骨细胞中的 SMAD 信号通路直接诱导 Notch 效应分子 Hes1

骨形态发生蛋白 (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 是一种具有基本螺旋-环-螺旋 (bHLH) 结构域的转录调节因子，是众所周知的 Notch 信号效应器。在这里，我们发现 BMP9 诱导成骨细胞中 Hes1 mRNA 和蛋白质表达的周期性增加，大概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）的过表达显着抑制。荧光素酶和染色质免疫沉淀分析表明，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 信号通路诱导成骨细胞中 Hes1 的表达。

更新日期：2020-12-25

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