Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
Biochem Biophys Res Commun. 2014 Jan 3;443(1):333-8. doi: 10.1016/j.bbrc.2013.11.121. Epub 2013 Dec 6.
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.
内质网（ER）应激抑制成骨细胞分化。激活转录因子（ATF）3 是 ATF/cAMP 反应元件结合蛋白家族转录因子的成员之一，它可被多种刺激诱导，包括细胞因子、激素、DNA 损伤和 ER 应激。然而，ATF3 在成骨细胞分化中的作用尚未阐明。用衣霉素（TM）处理，一种 ER 应激诱导剂，可增加前成骨细胞系 MC3T3-E1 中的 ATF3 表达。过表达 ATF3 抑制骨形态发生蛋白 2 刺激的碱性磷酸酶（ALP）的表达和激活，ALP 是成骨标志物。此外，用 shRNA 沉默 ATF3 可挽救 TM 处理对 ALP 表达的抑制。综上所述，这些数据表明 ATF3 是成骨细胞分化的一种新型负调节剂，通过特异性抑制前成骨细胞中 ALP 基因的表达来实现。
