title: ER stress-inducible ATF3 suppresses BMP2-induced ALP expression and activation in MC3T3-E1 cells.
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.
authors: Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea. Electronic address: myfreeJK@kribb.re.kr.
authors: Jae-kyung
authors: JK
authors: Park
authors: 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. Electronic address: Janghoon@kribb.re.kr.
authors: Hoon
authors: H
authors: Jang
authors: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea. Electronic address: hwangss@korea.kr.
authors: SeongSoo
authors: S
authors: Hwang
authors: Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea. Electronic address: eunjungk@paran.com.
authors: Eun-Jung
authors: EJ
authors: Kim
authors: Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea. Electronic address: pawust86@kribb.re.kr.
authors: Dong-Ern
authors: DE
authors: Kim
authors: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea. Electronic address: keonoh@korea.kr.
authors: Keon-Bong
authors: KB
authors: Oh
authors: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea. Electronic address: daejinkwon@gmail.com.
authors: Dae-Jin
authors: DJ
authors: Kwon
authors: Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: jtkoh@chonnam.ac.kr.
authors: Jeong-Tae
authors: JT
authors: Koh
authors: Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan.
authors: Kumi
authors: K
authors: Kimura
authors: Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. Electronic address: inoue-h@staff.kanazawa-u.ac.kr.
authors: Hiroshi
authors: H
authors: Inoue
authors: Department of Biotechnology, School of Engineering, Daegu University, Gyeongbuk 712-714, Republic of Korea. Electronic address: jangwg@daegu.ac.kr.
authors: Won-Gu
authors: WG
authors: Jang
authors: 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. Electronic address: jwlee@kribb.re.kr.
authors: Jeong-Woong
authors: JW
authors: Lee
mesh_terms: D051700:Activating Transcription Factor 3 / Q000096:biosynthesis* / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics*
chemical_list: D051700:Activating Transcription Factor 3; D048868:Adaptor Proteins, Signal Transducing; C103002:Atf3 protein, mouse; C480020:Atrnl1 protein, mouse; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D008565:Membrane Proteins
keywords: AA; AD-shATF3; ALP; ATF; Activating transcription factor 3 (ATF3); BMP2; Bone morphogenetic protein 2 (BMP2); CREB; ER; MOI; OC; Osteoblast differentiation; TM; Tunicamycin; activating transcription factor; alkaline phosphatase; anti-ATF3 shRNA; ascorbic acid 2-phosphate; bone morphogenetic protein-2; cAMP response element-binding; endoplasmic reticulum; multiplicity of infection; osteocalcin; tunicamycin; β-GP; β-glycerophosphate