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Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts
Author(s) -
Seong ChangHwan,
Chiba Norika,
Kusuyama Joji,
Subhan Amir Muhammad,
Eiraku Nahoko,
Yamashita Sachiko,
Ohnishi Tomokazu,
Nakamura Norifumi,
Matsuguchi Tetsuya
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14016
Subject(s) - hes1 , smad , microbiology and biotechnology , autocrine signalling , notch signaling pathway , bone morphogenetic protein , signal transduction , chemistry , effector , bone morphogenetic protein 2 , biology , biochemistry , receptor , gene , in vitro
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.