title: FGF2 Stimulates COUP-TFII Expression via the MEK1/2 Pathway to Inhibit Osteoblast Differentiation in C3H10T1/2 Cells.
abstract: Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor that regulates many key biological processes, including organ development and cell fate determination. Although the biological functions of COUP-TFII have been studied extensively, little is known about what regulates its gene expression, especially the role of inducible extracellular factors in triggering it. Here we report that COUP-TFII expression is regulated specifically by fibroblast growth factor 2 (FGF2), which mediates activation of the MEK1/2 pathway in mesenchymal lineage C3H10T1/2 cells. Although FGF2 treatment increased cell proliferation, the induction of COUP-TFII expression was dispensable. Instead, FGF2-primed cells in which COUP-TFII expression was induced showed a low potential for osteoblast differentiation, as evidenced by decreases in alkaline phosphatase activity and osteogenic marker gene expression. Reducing COUP-TFII by U0126 or siRNA against COUP-TFII prevented the anti-osteogenic effect of FGF2, indicating that COUP-TFII plays a key role in the FGF2-mediated determination of osteoblast differentiation capability. This report is the first to suggest that FGF2 is an extracellular inducer of COUP-TFII expression and may suppress the osteogenic potential of mesenchymal cells by inducing COUP-TFII expression prior to the onset of osteogenic differentiation.
authors.affiliation: Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.affiliation: Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Sin-Hye
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Yun-Chan
authors.initials: YC
authors.lastname: Hwang
authors.affiliation: Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Koh
mesh_terms: D016475:3T3 Cells; D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D013997:Time Factors
chemical_list: D051837:COUP Transcription Factor II; D016222:Fibroblast Growth Factor 2; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482129:Map2k2 protein, mouse