Genome-wide microRNA and gene analysis of mesenchymal stem cell chondrogenesis identifies an essential role and multiple targets for miR-140-5p

Barter, Matt J., Tselepi, Maria, Gómez, Rodolfo, Woods, Steven, Hui, Wang, Smith, Graham R., Shanley, Daryl P., Clark, Ian M. and Young, David A. (2015) Genome-wide microRNA and gene analysis of mesenchymal stem cell chondrogenesis identifies an essential role and multiple targets for miR-140-5p. Stem Cells, 33 (11). pp. 3266-3280. ISSN 1066-5099

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microRNAs (miRNAs) are abundantly expressed in development where they are critical determinants of cell differentiation and phenotype. Accordingly miRNAs are essential for normal skeletal development and chondrogenesis in particular. However, the question of which miRNAs are specific to the chondrocyte phenotype has not been fully addressed. Using microarray analysis of miRNA expression during mesenchymal stem cell chondrogenic differentiation and detailed examination of the role of essential differentiation factors, such as SOX9, TGF-b, and the cell condensation phase, we characterize the repertoire of specific miRNAs involved in chondrocyte development, highlighting in particular miR-140 and miR-455. Further with the use of mRNA microarray data we integrate miRNA expression and mRNA expression during chondrogenesis to underline the particular importance of miR-140, especially the -5p strand. We provide a detailed identification and validation of direct targets of miR-140-5p in both chondrogenesis and adult chondrocytes with the use of microarray and 30 UTR analysis. This emphasizes the diverse array of targets and pathways regulated by miR-140-5p. We are also able to confirm previous experimentally identified targets but, additionally, identify a novel positive regulation of the Wnt signaling pathway by miR-140-5p. Wnt signaling has a complex role in chondrogenesis and skeletal development and these findings illustrate a previously unidentified role for miR-140-5p in regulation of Wnt signaling in these processes. Together these developments further highlight the role of miRNAs during chondrogenesis to improve our understanding of chondrocyte development and guide cartilage tissue engineering.

Item Type: Article
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: mesenchymal stem cells,mirna,chondrogenesis,gene expression,differentiation,epigenetics
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Pure Connector
Date Deposited: 11 Nov 2015 17:00
Last Modified: 21 Oct 2022 02:33
DOI: 10.1002/stem.2093

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