ER stress-inducible ATF3 suppresses BMP2-induced ALP expression and activation in MC3T3-E1 cells

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Title
ER stress-inducible ATF3 suppresses BMP2-induced ALP expression and activation in MC3T3-E1 cells
Author(s)
Jae Kyung Park; Hoon Jang; S Hwang; E J Kim; Dong Ern Kim; K B Oh; D J Kwon; J T Koh; K Kimura; H Inoue; W G Jang; Jeong Woong Lee
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 443, no. 1, pp. 333-338
Publication Year
2014
Abstract
Endoplasmic reticulum (ER) stress suppresses osteoblast differentiation. Activating transcription factor (ATF) 3, a member of the ATF/cAMP response element-binding protein family of transcription factors, is induced by various stimuli including cytokines, hormones, DNA damage, and ER stress. However, the role of ATF3 in osteoblast differentiation has not been elucidated. Treatment with tunicamycin (TM), an ER stress inducer, increased ATF3 expression in the preosteoblast cell line, MC3T3-E1. Overexpression of ATF3 inhibited bone morphogenetic protein 2-stimulated expression and activation of alkaline phosphatase (ALP), an osteogenic marker. In addition, suppression of ALP expression by TM treatment was rescued by silencing of ATF3 using shRNA. Taken together, these data indicate that ATF3 is a novel negative regulator of osteoblast differentiation by specifically suppressing ALP gene expression in preosteoblasts.
Keyword
Activating transcription factor 3 (ATF3)
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2013.11.121
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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