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Epigenetic priming confers direct cell trans-differentiation from adipocyte to osteoblast in a transgene-free state
Cited 16 time in
Web of Science
Cited 17 time in Scopus
- Authors
- Issue Date
- 2016-07
- Publisher
- John Wiley & Sons Inc.
- Citation
- Journal of Cellular Physiology, Vol.231 No.7, pp.1484-1494
- Abstract
- The bone marrow of healthy individuals is primarily composed of osteoblasts and hematopoietic cells, while that of osteoporosis patients has a larger portion of adipocytes. There is evidence that the epigenetic landscape can strongly influence cell differentiation. We have shown that it is possible to direct the trans-differentiation of adipocytes to osteoblasts by modifying the epigenetic landscape with a DNA methyltransferase inhibitor (DNMTi), 5-aza-dC, followed by Wnt3a treatment to signal osteogenesis. Treating 3T3-L1 adipocytes with 5-aza-dC induced demethylation in the hypermethylated CpG regions of bone marker genes; subsequent Wnt3a treatment drove the cells to osteogenic differentiation. When old mice with predominantly adipose marrow were treated with both 5-aza-dC and Wnt3a, decreased fatty tissue and increased bone volume were observed. Together, our results indicate that epigenetic modification permits direct programming of adipocytes into osteoblasts in a mouse model of osteoporosis, suggesting that this approach could be useful in bone tissue-engineering applications. J. Cell. Physiol. 231: 1484-1494, 2016.
- ISSN
- 0021-9541
- Language
- English
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