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Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts

Cited 47 time in Web of Science Cited 50 time in Scopus
Authors
Kim, Sang Wan; Her, Sun Ju; Kim, Seong Yeon; Shin, Chan Soo
Issue Date
2005-01-15
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 2005 Feb 18;327(3):811-9.
Keywords
1-Methyl-3-isobutylxanthine/pharmacology3T3 CellsAdipocytes/*metabolismAlkaline Phosphatase/metabolismAnimalsBase SequenceCCAAT-Enhancer-Binding Protein-alpha/metabolismCell Differentiation/*physiologyCells, CulturedDexamethasone/pharmacologyGene Expression RegulationInsulin/metabolismMiceOsteoblasts/*cytologyPPAR gamma/metabolismPhenotypeTranscription Factors/genetics/*physiology
Abstract
Osteoblasts and adipocytes originate from common mesenchymal progenitor cells. We have investigated whether mouse osteoblastic MC3T3-E1 cells can be induced to transdifferentiate into mature adipocytes by the ectopic expression of adipogenic transcription factors, PPARgamma, C/EBPalpha, or both. Retrovirus-mediated overexpression of PPARgamma alone or both PPARgamma and C/EBPalpha resulted in reduced alkaline phosphatase activity and osteoblast-specific gene expression. Moreover, foci of adipocytes were identified in conditions favoring osteoblastic maturation. Upon treatment with insulin, dexamethasone, and IBMX, cells overexpressing PPARgamma alone or both PPARgamma and C/EBPalpha showed marked transdifferentiation to mature adipocytes expressing molecular markers of adipocytes. Cells expressing both PPARgamma and C/EBPalpha showed more robust phenotype of adipocytes than the cells expressing PPARgamma alone. Overexpression of C/EBPalpha alone did not result in adipogenesis. These results suggest that PPARgamma is a key molecular switch for the transdifferentiation to adipocytes whereas C/EBPalpha may differentiate MC3T3-E1 cells into osteoblasts and adipocytes.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15649418

http://hdl.handle.net/10371/22149
DOI
https://doi.org/10.1016/j.bbrc.2004.12.076
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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