title: Down-regulation of type I Runx2 mediated by dexamethasone is required for 3T3-L1 adipogenesis.
abstract: Runx2, a runt-related transcriptional factor family member, is involved in the regulation of osteoblast differentiation. Interestingly, it is abundant in growth-arrested 3T3-L1 preadipocytes and was dramatically down-regulated during adipocyte differentiation. Knockdown of Runx2 expression promoted 3T3-L1 adipocyte differentiation, whereas overexpression inhibited adipocyte differentiation and promoted the trans-differentiation of 3T3-L1 preadipocytes to bone cells. Runx2 was down-regulated specifically by dexamethasone (DEX). Only type I Runx2 was expressed in 3T3-L1 preadipocytes. Using luciferase assay and chromatin immunoprecipitation-quantitative PCR analysis, it was found that DEX repressed this type of Runx2 at the transcriptional level through direct binding of the glucocorticoid receptor (GR) to a GR-binding element in the Runx2 P2 promoter. Further studies indicated that GR recruited histone deacetylase 1 to the Runx2 P2 promoter which then mediated the deacetylation of histone H4 and down-regulated Runx2 expression. Runx2 might play its repressive role through the induction of p27 expression, which blocked 3T3-L1 adipocyte differentiation by inhibiting mitotic clonal expansion. Taken together, we identified Runx2 as a new downstream target of DEX and explored a new pathway between DEX, Runx2, and p27 which contributed to the mechanism of the 3T3-L1 adipocyte differentiation.
authors.affiliation: Key Laboratory of Molecular Medicine, the Ministry of Education; Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, PR China.
authors.forename: You-you
authors.initials: YY
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Shu-wen
authors.initials: SW
authors.lastname: Qian
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Qun
authors.initials: Q
authors.lastname: He
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Chun-gu
authors.initials: CG
authors.lastname: Ma
authors.forename: Qi-Qun
authors.initials: QQ
authors.lastname: Tang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D054338:Cell Transdifferentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; C493961:Cdkn1b protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; C493716:Runx2 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1