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Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts
Cited 50 time in
Web of Science
Cited 53 time in Scopus
- Authors
- Issue Date
- 2005-01-15
- Publisher
- Elsevier
- Citation
- Biochem Biophys Res Commun. 2005 Feb 18;327(3):811-9.
- Keywords
- 1-Methyl-3-isobutylxanthine/pharmacology ; 3T3 Cells ; Adipocytes/*metabolism ; Alkaline Phosphatase/metabolism ; Animals ; Base Sequence ; CCAAT-Enhancer-Binding Protein-alpha/metabolism ; Cell Differentiation/*physiology ; Cells, Cultured ; Dexamethasone/pharmacology ; Gene Expression Regulation ; Insulin/metabolism ; Mice ; Osteoblasts/*cytology ; PPAR gamma/metabolism ; Phenotype ; Transcription 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
https://hdl.handle.net/10371/22149
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