title: Long Non-coding RNA H19 Inhibits Adipocyte Differentiation of Bone Marrow Mesenchymal Stem Cells through Epigenetic Modulation of Histone Deacetylases.
abstract: Bone marrow mesenchymal stem cells (BMSCs) exhibit an increased propensity toward adipocyte differentiation accompanied by a reduction in osteogenesis in osteoporotic bone marrow. However, limited knowledge is available concerning the role of long non-coding RNAs (lncRNAs) in the differentiation of BMSCs into adipocytes. In this study, we demonstrated that lncRNA H19 and microRNA-675 (miR-675) derived from H19 were significantly downregulated in BMSCs that were differentiating into adipocytes. Overexpression of H19 and miR-675 inhibited adipogenesis, while knockdown of their endogenous expression accelerated adipogenic differentiation. Mechanistically, we found that miR-675 targeted the 3' untranslated regions of the histone deacetylase (HDAC) 4-6 transcripts and resulted in deregulation of HDACs 4-6, essential molecules in adipogenesis. In turn, trichostatin A, an HDAC inhibitor, significantly reduced CCCTC-binding factor (CTCF) occupancy in the imprinting control region upstream of the H19 gene locus and subsequently downregulated the expression of H19. These results show that the CTCF/H19/miR-675/HDAC regulatory pathway plays an important role in the commitment of BMSCs into adipocytes.
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Chanyuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.|Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Lingfei
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.|National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
authors.forename: Weiran
authors.initials: W
authors.lastname: Li
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D015870:Gene Expression; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
chemical_list: C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D006655:Histone Deacetylases