Adipogenic differentiation of human mesenchymal stromal cells is down-regulated by microRNA-369-5p and up-regulated by microRNA-371

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...

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Hauptverfasser: Bork, Simone (VerfasserIn) , Horn, Patrick (VerfasserIn) , Castoldi, Mirco (VerfasserIn) , Hellwig, Isabelle (VerfasserIn) , Ho, Anthony Dick (VerfasserIn) , Wagner, Wolfgang (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2011
In: Journal of cellular physiology
Year: 2011, Jahrgang: 226, Heft: 9, Pages: 2226-2234
ISSN:1097-4652
DOI:10.1002/jcp.22557
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/jcp.22557
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.22557
Volltext
Verfasserangaben:Simone Bork, Patrick Horn, Mirco Castoldi, Isabelle Hellwig, Anthony D. Ho, and Wolfgang Wagner

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520 |a 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. J. Cell. Physiol. 226: 2226-2234, 2011. © 2010 Wiley-Liss, Inc. 
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