title: A regulatory loop containing miR-26a, GSK3β and C/EBPα regulates the osteogenesis of human adipose-derived mesenchymal stem cells.
abstract: Elucidating the molecular mechanisms responsible for osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) will provide deeper insights into the regulatory mechanisms of this process and help develop more efficient methods for cell-based therapies. In this study, we analysed the role of miR-26a in the regulation of hADSC osteogenesis. The endogenous expression of miR-26a increased during the osteogenic differentiation. The overexpression of miR-26a promoted hADSC osteogenesis, whereas osteogenesis was repressed by miR-26a knockdown. Additionally, miR-26a directly targeted the 3'UTR of the GSK3β, suppressing the expression of GSK3β protein. Similar to the effect of overexpressing miR-26a, the knockdown of GSK3β promoted osteogenic differentiation, whereas GSK3β overexpression inhibited this process, suggesting that GSK3β acted as a negative regulator of hADSC osteogenesis. Furthermore, GSK3β influences Wnt signalling pathway by regulating β-catenin, and subsequently altered the expression of its downstream target C/EBPα. In turn, C/EBPα transcriptionally regulated the expression of miR-26a by physically binding to the CTDSPL promoter region. Taken together, our data identified a novel feedback regulatory circuitry composed of miR-26a, GSK3β and C/EBPα, the function of which might contribute to the regulation of hADSC osteogenesis. Our findings provided new insights into the function of miR-26a and the mechanisms underlying osteogenesis of hADSCs.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Wodong
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions; D000273:Adipose Tissue / Q000166:cytology; D001483:Base Sequence; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050659:Core Binding Factor Alpha 1 Subunit; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D051176:beta Catenin; C528163:MIRN26 microRNA, human; C000605506:GSK3B protein, human