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Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation
Author(s) -
Ann EunJung,
Kim HwaYoung,
Choi YunHee,
Kim MiYeon,
Mo JungSoon,
Jung Jane,
Yoon JiHye,
Kim SuMan,
Moon JeongSik,
Seo MiSun,
Hong JiAe,
Jang WonGu,
Shore Paul,
Komori Toshihisa,
Koh JeongTae,
Park HeeSae
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.227
Subject(s) - runx2 , osteoblast , downregulation and upregulation , hes1 , signal transduction , cellular differentiation , microbiology and biotechnology , biology , notch signaling pathway , chemistry , gene , biochemistry , in vitro
Notch1 genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch1 signaling in osteogenesis is not well defined. Notch1 controls osteoblast differentiation by affecting Runx2, but the question arises whether normal osteoblastic differentiation can occur regardless of the presence of Notch1. In this study, we observed the downregulation of Notch1 signaling during osteoblastic differentiation. BMPR‐IB/Alk6‐induced Runx2 proteins reduced Notch1 activity to a marked degree. Accumulated Runx2 suppressed Notch1 transcriptional activity by dissociating the Notch1‐IC‐RBP‐Jk complex. Using deletion mutants, we also determined that the N‐terminal domain of Runx2 was crucial to the binding and inhibition of the N‐terminus of the Notch1 intracellular domain. Notably, upregulation of the Runx2 protein level paralleled reduced expression of Hes1, which is a downstream target of Notch1, during osteoblast differentiation. Collectively, our data suggest that Runx2 is an inhibitor of the Notch1 signaling pathway during normal osteoblast differentiation. © 2011 American Society for Bone and Mineral Research.