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

Journal of Cellular Physiology
Young-Dan ChoHyun-Mo Ryoo

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.

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Citations

Jan 13, 2017·Journal of Dental Research·Y ChoH Ryoo
Jan 5, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Han-Sol BaeHyun-Mo Ryoo
Feb 10, 2017·Journal of Cellular Physiology·Giulia MauriziAntonella Poloni
Dec 30, 2017·Bone Research·Chengde GaoCijun Shuai
Aug 17, 2018·Current Stem Cell Research & Therapy·Young-Dan ChoYang-Jo Seol
Mar 23, 2018·Journal of Bone Metabolism·Young-Dan Cho, Hyun-Mo Ryoo
Jan 29, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Feng-Sheng WangJih-Yang Ko
Nov 5, 2020·Journal of Dental Research·H YoonH M Ryoo
Mar 7, 2021·International Journal of Molecular Sciences·Young-Dan ChoHyun-Mo Ryoo
Jan 29, 2019·Journal of Molecular and Cellular Cardiology·Keith Al-HasaniAssam El-Osta

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