title: Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation.
abstract: 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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Ann
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Jung-Soon
authors.initials: JS
authors.lastname: Mo
authors.forename: Jane
authors.initials: J
authors.lastname: Jung
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yoon
authors.forename: Su-Man
authors.initials: SM
authors.lastname: Kim
authors.forename: Jeong-Sik
authors.initials: JS
authors.lastname: Moon
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Seo
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Hong
authors.forename: Won-Gu
authors.initials: WG
authors.lastname: Jang
authors.forename: Paul
authors.initials: P
authors.lastname: Shore
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Koh
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology*; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; C493709:RUNX2 protein, human; D051881:Receptor, Notch1; C493716:Runx2 protein, mouse