title: Enhancer of Zeste Homolog 2 and Histone Deacetylase 9c Regulate Age-Dependent Mesenchymal Stem Cell Differentiation into Osteoblasts and Adipocytes.
abstract: Mesenchymal stem cells (MSCs) are multipotent precursors that can undergo multilineage differentiation, including osteogenesis and adipogenesis, which are two mutually exclusive events. Previously, we demonstrated that enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, mediates epigenetic silencing of histone deacetylase 9c (HDAC9c) in adipocytes but not in osteoblasts and that HDAC9c accelerates osteogenesis while attenuating adipogenesis of MSCs through inactivation of peroxisome proliferator-activated receptor gamma 2 activity. Importantly, disrupting the balance between adipogenesis and osteogenesis can lead to age-associated bone loss (osteoporosis) and obesity. Here, we investigated the relationship between age, and osteogenic and adipogenic differentiation potential of MSCs by comparing EZH2 and HDAC9c expression in osteoblasts and adipocytes of both human and mice origins to determine whether the EZH2-HDAC9c axis regulates age-associated osteoporosis and obesity. Our findings indicated that a decline in HDAC9c expression over time was accompanied by increased EZH2 expression and suggested that a therapeutic intervention for age-associated osteoporosis and obesity may be feasible by targeting the EZH2-HDAC9c axis. Stem Cells 2016;34:2183-2193.
authors.affiliation: Graduate Institute of Cancer Biology, College of Medicine, Taichung, Taiwan.|Cancer Biology and Drug Discovery Ph.D. Program, College of Medicine, China Medical University, Taichung, Taiwan.|Center for Molecular Medicine, Taichung, Taiwan.
authors.forename: Ya-Huey
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Center for Molecular Medicine, Taichung, Taiwan.
authors.forename: Chiao-Chen
authors.initials: CC
authors.lastname: Chung
authors.affiliation: Graduate Institute of Cancer Biology, College of Medicine, Taichung, Taiwan.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Su-Peng
authors.initials: SP
authors.lastname: Yeh
authors.affiliation: Department of Molecular and Cellular Oncology, the University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Cancer Biology, College of Medicine, Taichung, Taiwan.|Center for Molecular Medicine, Taichung, Taiwan.|Department of Molecular and Cellular Oncology, the University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
authors.affiliation: Graduate Institute of Cancer Biology, College of Medicine, Taichung, Taiwan.|Center for Molecular Medicine, Taichung, Taiwan.|Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.|Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Long-Yuan
authors.initials: LY
authors.lastname: Li
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002648:Child; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D012097:Repressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012097:Repressor Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; C486544:HDAC9 protein, human; C486545:Hdac9 protein, mouse; D006655:Histone Deacetylases
keywords: Adipogenesis; Aging; EZH2; HDAC9c; Mesenchymal stem cells; Osteogenesis