title: GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2.
abstract: Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2.
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine, Ajou University, Suwon 443-721, Korea.
authors.forename: Insun
authors.initials: I
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Kabsun
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Pharmacology; Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine; Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-721, Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine; Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-721, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine; Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-721, Korea.
authors.forename: Hae-Ok
authors.initials: HO
authors.lastname: Byun
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine; Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-721, Korea.
authors.forename: Gyesoon
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Pharmacology; Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, Korea.
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D050991:GATA4 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C501120:Dlx5 protein, mouse; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015675:Osteocalcin; D000469:Alkaline Phosphatase