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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / cytology
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Adipocytes / drug effects*
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Adipogenesis / drug effects*
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Cell Transdifferentiation / drug effects
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Core Binding Factor Alpha 1 Subunit / antagonists & inhibitors
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Core Binding Factor Alpha 1 Subunit / genetics
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Core Binding Factor Alpha 1 Subunit / metabolism*
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Cyclin-Dependent Kinase Inhibitor p27 / antagonists & inhibitors
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Dexamethasone / pharmacology*
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Down-Regulation / drug effects*
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Histone Deacetylase 1 / antagonists & inhibitors
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Histone Deacetylase 1 / genetics
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Histone Deacetylase 1 / metabolism
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Mice
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Osteoblasts / cytology
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Osteoblasts / drug effects
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Osteoblasts / metabolism
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Promoter Regions, Genetic / drug effects
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering
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Receptors, Glucocorticoid / antagonists & inhibitors
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / metabolism
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Response Elements / drug effects
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Up-Regulation / drug effects
Substances
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Anti-Inflammatory Agents
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Cdkn1b protein, mouse
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Core Binding Factor Alpha 1 Subunit
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Protein Isoforms
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RNA, Messenger
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RNA, Small Interfering
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Receptors, Glucocorticoid
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Recombinant Proteins
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Runx2 protein, mouse
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Cyclin-Dependent Kinase Inhibitor p27
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Dexamethasone
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Hdac1 protein, mouse
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Histone Deacetylase 1