title: Serum Deprivation-Induced Human GM3 Synthase (hST3Gal V) Gene Expression Is Mediated by Runx2 in Human Osteoblastic MG-63 Cells.
abstract: Serum deprivation (SD) is well known to induce G0/G1 cell cycle arrest and apoptosis in various cells. In the present study, we firstly found that SD could induce G1 arrest and the differentiation of human osteoblastic MG-63 cells, as evidenced by the increase of osteoblastic differentiation markers, such as bone morphogenetic protein-2 (BMP-2), osteocalcin and runt-related transcription factor 2 (Runx2). In parallel, gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 biosynthesis was upregulated by SD in MG-63 cells. The 5'-flanking region of the hST3Gal V gene was functionally characterized to elucidate transcriptional regulation of hST3Gal V in SD-induced MG-63 cells. Promoter analysis using 5'-deletion constructs of the hST3Gal V gene demonstrated that the -432 to -177 region functions as the SD-inducible promoter. Site-directed mutagenesis revealed that the Runx2 binding sites located side-by-side at positions -232 and -222 are essential for the SD-induced expression of hST3Gal V in MG-63 cells. In addition, the chromatin immunoprecipitation assay also showed that Runx2 specifically binds to the hST3Gal V promoter region containing Runx2 binding sites. These results suggest that SD triggers upregulation of hST3Gal V gene expression through Runx2 activation by BMP signaling in MG-63 cells.
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. gusrud073@naver.com.
authors.forename: Hyun-Kyoung
authors.initials: HK
authors.lastname: Yoon
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. jwlee0203@dgist.ac.kr.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. kskim@dau.ac.kr.
authors.forename: Kyoung-Sook
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. ss11033@hanmail.net.
authors.forename: Seo-Won
authors.initials: SW
authors.lastname: Mun
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. mose79@dau.ac.kr.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, College of Medicine, Dong-A University, Busan 604-714, Korea. hyeonjun@dau.ac.kr.
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, Kyunggi-Do 440-746, Korea. chkimbio@skku.edu.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 604-714, Korea. yclee@dau.ac.kr.
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
mesh_terms: D024506:5' Flanking Region; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology; D012799:Sialyltransferases / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D012799:Sialyltransferases; C021343:haematoside synthetase
keywords: MG-63 cells; human GM3 synthase (hST3Gal V); runt-related transcription factor 2 (Runx2); serum deprivation; transcriptional regulation