title: MicroRNAs miR-96, miR-124, and miR-199a regulate gene expression in human bone marrow-derived mesenchymal stem cells.
abstract: MicroRNAs are small non-coding RNAs that control gene expression at the post-transcriptional level by binding to 3'-untranslated regions (3'-UTR) of their target mRNAs. They present a promising tool to delineate the molecular mechanisms regulating differentiation of human mesenchymal stromal cells (hMSCs) and to improve the controlled differentiation of hMSCs in therapeutic applications. Here we show that three microRNAs, miR-96, miR-124, and miR-199a, were differentially expressed during osteogenic, adipogenic, and chondrogenic induction of human bone marrow-derived MSCs. miR-96 expression was increased during osteogenesis and adipogenesis, but not during chondrogenesis. miR-124 was exclusively expressed in adipocytes, whereas miR-199a was upregulated in osteoblasts and chondrocytes. Furthermore, functional studies with synthetic miRNA precursors and inhibitors demonstrated that miR-96, miR-124, and miR-199a regulated the expression of genes important for hMSC differentiation, such as aggrecan, transcription factor SOX9, and fatty acid binding protein 4 (FABP4). Modulation of miR-96, miR-124, and miR-199a expression may thus be useful in specific targeting of hMSC differentiation, for e.g., MSC-based therapies. J
authors.affiliation: Skeletal Biology Consortium, Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. sksuom@utu.fi
authors.forename: Salla K
authors.initials: SK
authors.lastname: Laine
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Alm
authors.forename: Sanna P
authors.initials: SP
authors.lastname: Virtanen
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Aro
authors.forename: Tiina K
authors.initials: TK
authors.lastname: Laitala-Leinonen
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000235:genetics
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C509207:MIRN124 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C531408:mirn199 microRNA, human