@phdthesis{oai:ir.kagoshima-u.ac.jp:00016101, author = {成, 昌奐 and Seong, Chang-Hwan}, month = {2022-07-28, 2022-07-28, 2022-05-27, 2022-05-27}, note = {博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨, 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. This is the peer reviewed version of the following article: Chang-Hwan Seong, Norika Chiba, Joji Kusuyama, Muhammad Subhan Amir, Nahoko Eiraku, Sachiko Yamashita, Tomokazu Ohnishi, Norifumi Nakamura, Tetsuya Matsuguchi Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts FEBS Letters 595(3), p.389–403, 2020, which has been published in final form at https://doi.org/10.1002/1873-3468.14016. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.}, school = {鹿児島大学}, title = {Bone morphogenetic protein 9 (BMP9) directly induces Notch effector molecule Hes1 through the SMAD signaling pathway in osteoblasts}, year = {} }