Premium
Distal‐less homeobox 5 inhibits adipogenic differentiation through the down‐regulation of peroxisome proliferator‐activated receptor γ expression
Author(s) -
Lee HyeLim,
Woo Kyung Mi,
Ryoo HyunMo,
Baek JeongHwa
Publication year - 2013
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24106
Subject(s) - dlx5 , adipogenesis , osteoblast , microbiology and biotechnology , cellular differentiation , biology , homeobox , gene knockdown , homeobox a1 , peroxisome proliferator activated receptor , transcription factor , medicine , endocrinology , chemistry , mesenchymal stem cell , receptor , biochemistry , gene , in vitro
Distal‐less homeobox 5 (Dlx5) is a positive regulator of osteoblast differentiation that contains a homeobox domain. Because there are possible reciprocal relationships between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (MSCs), we examined the regulatory role of Dlx5 in adipogenic differentiation in this study. Adipogenic stimuli suppressed the expression levels of Dlx5 mRNA in mouse bone marrow stromal cells. Over‐expression of Dlx5 inhibited adipogenic differentiation in human bone marrow MSCs and 3T3‐L1 preadipocytic cells whereas knockdown of Dlx5 enhanced adipogenic differentiation in 3T3‐L1 cells. Over‐expression of Dlx5 suppressed the expression of adipogenic marker genes, including CCAAT/enhancer‐binding protein α (C/EBPα) and peroxisome proliferator‐activated receptor γ (PPARγ). Dlx5‐mediated suppression of adipogenic differentiation was overcome by over‐expression of PPARγ but not by that of cAMP response element binding protein (CREB) or C/EBPα. Dlx5 decreased the transcriptional activity of CREB and C/EBPα in a dose‐dependent manner. Dlx5 directly bound to CREB and C/EBPα and prevented them from binding to and subsequently transactivating the PPARγ promoter. These results suggest that Dlx5 plays an important regulatory role in fate determination of bone marrow MSCs toward the osteoblast lineage through the inhibition of adipocyte differentiation as well as the direct stimulation of osteoblast differentiation. J. Cell. Physiol. 228: 87–98, 2013. © 2012 Wiley Periodicals, Inc.