Down-regulation of type I Runx2 mediated by dexamethasone is required for 3T3-L1 adipogenesis

You You Zhang, Xi Li, Shu Wen Qian, Liang Guo, Hai Yan Huang, Qun He, Yuan Liu, Chun Gu Ma, Qi Qun Tang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)798-808
Number of pages11
JournalMolecular Endocrinology
Volume26
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Zhang, Y. Y., Li, X., Qian, S. W., Guo, L., Huang, H. Y., He, Q., Liu, Y., Ma, C. G., & Tang, Q. Q. (2012). Down-regulation of type I Runx2 mediated by dexamethasone is required for 3T3-L1 adipogenesis. Molecular Endocrinology, 26(5), 798-808. https://doi.org/10.1210/me.2011-1287