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Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation

✍ Scribed by 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

Publisher: American Society for Bone and Mineral Research
Year: 2011
Tongue: English
Weight: 1005 KB
Volume: 26
Category: Article
ISSN: 0884-0431
DOI: 10.1002/jbmr.227

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✦ Synopsis

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. © 2011 American Society for Bone and Mineral Research.

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