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Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation.
MedLine Citation:
PMID:  20740684     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Eun-Jung Ann; Hwa-Young Kim; Yun-Hee Choi; Mi-Yeon Kim; Jung-Soon Mo; Jane Jung; Ji-Hye Yoon; Su-Man Kim; Jeong-Sik Moon; Mi-Sun Seo; Ji-Ae Hong; Won-Gu Jang; Paul Shore; Toshihisa Komori; Jeong-Tae Koh; Hee-Sae Park
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  26     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  317-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Society for Bone and Mineral Research.
Affiliation:
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
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