title: Osterix plays a critical role in BMP4-induced promoter activity of connexin43.
abstract: Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression was significantly repressed by the addition of shRNA against Osterix, whereas overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore, Osterix directly occupied the promoter region of Cx43 and subsequently increased Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation of the Ser76 and Ser80 residues in Osterix were found to be critical for its activity on the Cx43 promoter. Our results suggest that Osterix plays an important role in increasing bone morphogenetic protein 4-induced Cx43 activity.
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors: Younho
authors: Y
authors: Han
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
authors: Dong Hyeok
authors: DH
authors: Cho
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea. Electronic address: djchung@chonnam.ac.kr.
authors: Dong Jin
authors: DJ
authors: Chung
authors: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea. Electronic address: kwanglee@chonnam.ac.kr.
authors: Kwang Youl
authors: KY
authors: Lee
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D018031:Connexin 43; C500216:GJA1 protein, human; D034741:RNA, Small Interfering; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D008156:Luciferases
keywords: Bone; Connexin43 (Cx43); Osterix