Inhibition of Wnt/ß-catenin signaling by dexamethasone promotes adipocyte differentiation in mesenchymal progenitor cells, ROB-C26.
Histochem Cell Biol
; 138(6): 833-45, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-22886144
ABSTRACT
Dexamethasone (Dex) stimulates the differentiation of mesenchymal progenitor cells into adipocytes and osteoblasts. However, the mechanisms underlying Dex-induced differentiation have not been clearly elucidated. We examined the effect of Dex on the expression and activity of Wnt/ß-catenin signal-related molecules in a clonal mesenchymal progenitor cell line, ROB-C26 (C26). Dex induced the mRNA expression of Wnt antagonists, dickkopf-1 (Dkk-1), and Wnt inhibitory factor (WIF)-1. Immunocytochemical analysis showed that the downregulation of ß-catenin protein expression by Dex occured concomitantly with the increased expression of the PPARγ protein. Dex decreased phosphorylation of Ser9-GSK3ß and expression of active ß-catenin protein. To examine the effects of Dex on Wnt/ß-catenin activity, we used immunocytochemistry to analyze TCF/LEF-mediated transcription during Dex-induced adipogenesis in Wnt indicator (TOPEGFP) C26 cells. Our results demonstrated that Dex repressed TCF/LEF-mediated transcription, but induced adipocyte differentiation. Treatment with a GSK3ß inhibitor attenuated Dex-induced inhibition of TCF/LEF-mediated transcriptional activity, but suppressed Dex-induced adipocyte differentiation, indicating that adipocyte differentiation and inhibition of Wnt/ß-catenin activity by Dex are mediated by GSK3ß activity. Furthermore, ß-catenin knockdown not only suppressed Dex-induced ALP-positive osteoblasts differentiation but also promoted Dex-induced adipocytes differentiation. These results suggest that inhibition of ß-catenin expression by Dex promotes the differentiation of mesenchymal progenitor cells into adipocytes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dexamethasone
/
Signal Transduction
/
Adipocytes
/
Wnt Proteins
/
Beta Catenin
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Adipogenesis
/
Mesenchymal Stem Cells
Limits:
Animals
Language:
En
Journal:
Histochem Cell Biol
Journal subject:
CITOLOGIA
/
HISTOCITOQUIMICA
Year:
2012
Document type:
Article
Affiliation country:
Japón