The microRNA-29 family in cartilage homeostasis and osteoarthritis

Le, Linh TT, Swingler, Tracey E, Crowe, Natalie, Vincent, Tonia L, Barter, Matthew J, Donell, Simon T, Delany, Anne M, Dalmay, Tamas, Young, David A and Clark, Ian M (2016) The microRNA-29 family in cartilage homeostasis and osteoarthritis. Journal of Molecular Medicine, 94 (5). pp. 583-596. ISSN 1432-1440

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MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 04 Jan 2016 13:00
Last Modified: 22 Jul 2020 00:30
DOI: 10.1007/s00109-015-1374-z

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