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The microRNA-29 family in cartilage homeostasis and osteoarthritis

Lookup NU author(s): Dr Matthew Barter, 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 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 was also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGF beta 1 decreased expression of miR-29a, b, and c (3p) in primary chondrocytes, whilst IL-1 beta increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NF kappa B, and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, and 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.Expression of the miR-29 family is regulated in cartilage during osteoarthritis.SOX9 represses expression of the miR-29 family in chondrocytes.The miR-29 family is regulated by TGF-beta 1 and IL-1 in chondrocytes.The miR-29 family negatively regulates Smad, NF kappa B, and canonical Wnt signalling.Several Wnt-related genes are direct targets of the miR-29 family.


Publication metadata

Author(s): Le LTT, Swingler TE, Crowe N, Vincent TL, Barter MJ, Donell ST, Delany AM, Dalmay T, Young DA, Clark IM

Publication type: Article

Publication status: Published

Journal: Journal of Molecular Medicine

Year: 2016

Volume: 94

Issue: 5

Pages: 583-596

Print publication date: 01/05/2016

Online publication date: 19/12/2015

Acceptance date: 30/11/2015

Date deposited: 15/06/2016

ISSN (print): 0946-2716

ISSN (electronic): 1432-1440

Publisher: Springer

URL: http://dx.doi.org/10.1007/s00109-015-1374-z

DOI: 10.1007/s00109-015-1374-z


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