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

作者：Park Jae kyung; Jang Hoon; Hwang SeongSoo; Kim Eun Jung; Kim Dong Ern; Oh Keon Bong; Kwon Dae Jin; Koh Jeong Tae; Kimura Kumi; Inoue Hiroshi; Jang Won Gu^*; Lee Jeong Woong

来源：Biochemical and Biophysical Research Communications, 2014, 443(1): 333-338.

DOI：10.1016/j.bbrc.2013.11.121

• Activating transcription factor 3 (ATF3)
• Bone morphogenetic protein 2 (BMP2)
• Tunicamycin
• Osteoblast differentiation

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.

• 出版日期2014-1-3