Projects per year
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-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.
Original language | English |
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Pages (from-to) | 3266-3280 |
Number of pages | 15 |
Journal | Stem Cells |
Volume | 33 |
Issue number | 11 |
Early online date | 29 Jul 2015 |
DOIs | |
Publication status | Published - Nov 2015 |
Keywords
- Mesenchymal stem cells
- miRNA
- Chondrogenesis
- Gene expression
- Differentiation
- Epigenetics
Profiles
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Ian Clark
- School of Biological Sciences - Professor of Musculoskeletal Biology
- Musculoskeletal Medicine - Member
- Nutrition and Preventive Medicine - Member
- HealthUEA - Academic Chair
Person: Research Group Member, Academic, Teaching & Research
Projects
- 1 Finished
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The function of microRNAs in cartilage metabolism and osteoarthritis
Clark, I., Dalmay, T. & Swingler, T.
1/01/11 → 30/06/17
Project: Research