Epigenetic Priming Confers Direct Cell Trans-Differentiation From Adipocyte to Osteoblast in a Transgene-Free State

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• 作者：Young-Dan Cho ; Han-Sol Bae ; Dong-Seol Lee ; Won-Joon Yoon ; Kyung-Mi Woo ; Jeong-Hwa Baek ; Gene Lee ; Joo-Cheol Park ; Young Ku and Hyun-Mo Ryoo
• 刊名：Journal of Cellular Physiology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：231
• 期：7
• 页码：1484-1494
• 全文大小：1825K
• ISSN：1097-4652

文摘

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.