title: Adipogenic differentiation of human mesenchymal stromal cells is down-regulated by microRNA-369-5p and up-regulated by microRNA-371.
abstract: Long-term culture of human mesenchymal stromal cells (MSC) has implications on their proliferation and differentiation potential and we have demonstrated that this is associated with up-regulation of the five microRNAs miR-29c, miR-369-5p, miR-371, miR-499, and let-7f. In this study, we examined the role of these senescence-associated microRNAs for cellular aging and differentiation of MSC. Proliferation was reduced upon transfection with miR-369-5p, miR-371, and miR-499. Adipogenic differentiation was impaired by miR-369-5p whereas it was highly increased by miR-371. This was accompanied by respective gene expression changes of some adipogenic key molecules (adiponectin and fatty acid-binding protein 4 [FABP4]). Furthermore luciferase reporter assay indicated that FABP4 is a direct target of miR-369-5p. Microarray analysis upon adipogenic or osteogenic differentiation revealed down-regulation of several microRNAs albeit miR-369-5p and miR-371 were not affected. Expression of the de novo DNA methyltransferases DNMT3A and DNMT3B was up-regulated by transfection of miR-371 whereas expression of DNMT3A was down-regulated by miR-369-5p. In summary, we identified miR-369-5p and miR-371 as antagonistic up-stream regulators of adipogenic differentiation and this might be indirectly mediated by epigenetic modifications.
authors.affiliation: Department of Medicine V, University of Heidelberg, Heidelberg, Germany. simone.bork@med.uni-heidelberg.de
authors.forename: Simone
authors.initials: S
authors.lastname: Bork
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
authors.forename: Mirco
authors.initials: M
authors.lastname: Castoldi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hellwig
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D050156:Adipogenesis / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation / Q000235:genetics*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D050556:Fatty Acid-Binding Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C493410:FABP4 protein, human; C560308:MIRN369 microRNA, human; C554834:MIRN371 microRNA, human