Down-Regulation of Type I Runx2 Mediated by Dexamethasone Is Required for 3T3-L1 Adipogenesis

Author:

Zhang You-you12,Li Xi12,Qian Shu-wen1,Guo Liang1,Huang Hai-yan1,He Qun1,Liu Yuan1,Ma Chun-gu1,Tang Qi-Qun12

Affiliation:

1. Key Laboratory of Molecular Medicine (Y.Y.Z., X.L., L.G., H.Y.H., Q.H., Y.L., C.G.M., Q.Q.T.), the Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai 200032, P.R. China;

2. Institute of Stem Cell Research and Regenerative Medicine (Y.Y.Z., X.L., Q.Q.T.), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China

Abstract

AbstractRunx2, 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.

Publisher

The Endocrine Society

Subject

Endocrinology,Molecular Biology,General Medicine

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