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

Lookup NU author(s): Dr Matthew Barter, Maria Tselepi, Dr Rodolfo Gomez, Steven Woods, Dr Graham Smith, Dr Daryl Shanley, Professor David Young

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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-β and the cell condensation phase, we characterise 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 3’UTR analysis. This emphasises 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 signalling pathway by miR-140-5p. Wnt signalling 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 signalling 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.


Publication metadata

Author(s): Barter MJ, Tselepi M, Gomez R, Woods S, Hui W, Smith GR, Shanley DP, Clark IM, Young DA

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2015

Volume: 33

Issue: 11

Pages: 3266-3280

Print publication date: 01/11/2015

Online publication date: 29/07/2015

Acceptance date: 01/06/2015

Date deposited: 29/07/2015

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: http://dx.doi.org/10.1002/stem.2093

DOI: 10.1002/stem.2093

PubMed id: 26175215


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