Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Biol Pharm Bull ; 44(9): 1303-1308, 2021.
Article in English | MEDLINE | ID: mdl-34471058

ABSTRACT

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master transcription factor in adipocyte differentiation, while distal-less homeobox 5 (Dlx5) is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression. Considering that adipocytes and osteoblasts share common progenitors, there is a reciprocal correlation between bone and fat formation. However, the mechanism by which Dlx5 controls PPARγ remains unclear. We elucidated that Dlx5 physically binds to PPARγ during immunoprecipitation; in particular, the ligand-binding and DNA-binding domains of PPARγ were involved in the interaction. Transcriptional activity of PPARγ was significantly decreased by Dlx5 overexpression, whereas the opposite results were detected with Dlx5 knockdown. Rosiglitazone, a PPARγ agonist, further enhanced the PPARγ-induced transcriptional activity; however, Dlx5 overexpression effectively repressed the rosiglitazone-mediated increase in activity. Finally, DNA-binding affinity assay revealed that Dlx5 interrupts the interaction of PPARγ with the PPARγ response element promoter. In conclusion, our findings indicate that Dlx5 impedes PPARγ-induced activity, and it may be useful for managing diabetes drug-mediated obesity.


Subject(s)
Homeodomain Proteins/metabolism , PPAR gamma/metabolism , 3T3-L1 Cells , Adipocytes/physiology , Animals , Cell Differentiation/drug effects , Cell Differentiation/genetics , Mice , PPAR gamma/agonists , Promoter Regions, Genetic , Protein Domains , Rosiglitazone/pharmacology , Transcriptional Activation
2.
Sci Rep ; 6: 35655, 2016 10 18.
Article in English | MEDLINE | ID: mdl-27752121

ABSTRACT

Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). Further studies indicated that Osterix significantly decreased PPARγ-induced transcriptional activity. Using co-immunoprecipitation and GST-pull down analysis, we found that Osterix directly interacts with PPARγ. The ligand-binding domain (LBD) of PPARγ was responsible for this interaction, which was followed by repression of PPARγ-induced transcriptional activity, even in the presence of rosiglitazone. Taken together, we identified the Osterix has an important regulatory role on PPARγ activity, which contributed to the mechanism of adipogenesis.


Subject(s)
Adipocytes/physiology , Bone Marrow Cells/physiology , Mesenchymal Stem Cells/physiology , Osteoblasts/physiology , PPAR gamma/metabolism , Sp7 Transcription Factor/metabolism , Adipogenesis , Animals , Cell Differentiation , Cell Line , Mice , PPAR gamma/genetics , Protein Binding , RNA, Small Interfering/genetics , Sp7 Transcription Factor/genetics , Transcription, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...