Epigenetic Priming Confers Direct Cell Trans-Differentiation From Adipocyte to Osteoblast in a Transgene-Free State.
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.
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.|Department of Periodontology, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Young-Dan
YD
Cho
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Han-Sol
HS
Bae
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Dong-Seol
DS
Lee
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Won-Joon
WJ
Yoon
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Kyung-Mi
KM
Woo
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Jeong-Hwa
JH
Baek
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Gene
G
Lee
Department of Oral Histology-Developmental Biology, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Joo-Cheol
JC
Park
Department of Periodontology, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Young
Y
Ku
Department of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul, Korea.
Hyun-Mo
HM
Ryoo
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000235:genetics*; D003568:Cytidine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D060509:Wnt3A Protein / Q000235:genetics
D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C012201:5'-azacytidine 5'-monophosphate; D004248:DNA (Cytosine-5-)-Methyltransferases; D003568:Cytidine Monophosphate