Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts.
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.
Kim
Sang Wan
SW
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yungun-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea.
Her
Sun Ju
SJ
Kim
Seong Yeon
SY
Shin
Chan Soo
CS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D007328:Insulin / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology*; D047495:PPAR gamma / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D007328:Insulin; D047495:PPAR gamma; D014157:Transcription Factors; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D015056:1-Methyl-3-isobutylxanthine