Genome-wide microRNA and gene analysis of mesenchymal stem cell chondrogenesis identifies an essential role and multiple targets for miR-140-5p (2015)

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

    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.

      • Legacy Date: 01/11/2015
      • Journal: Stem Cells
      • Volume: 33
      • Issue: 11
      • Pages: 3266-3280
      • Publisher: AlphaMed Press, Inc.
      • Publication type: Article
      • Bibliographic status: Published

      Dr Daryl Shanley
      Director of CISBAN

      Dr Graham Smith
      Experimental Scientific Officer

      Professor David Young
      Professor of Musculoskeletal Biology