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Computer simulation models as a tool to investigate the role of microRNAs in osteoarthritis

Lookup NU author(s): Dr Carole Proctor, Dr Graham Smith

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


Abstract

© 2017 Proctor, Smith. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The aim of this study was to show how computational models can be used to increase our understanding of the role of microRNAs in osteoarthritis (OA) using miR-140 as an example. Bioinformatics analysis and experimental results from the literature were used to create and calibrate models of gene regulatory networks in OA involving miR-140 along with key regulators such as NF-κB, SMAD3, and RUNX2. The individual models were created with the modelling standard, Systems Biology Markup Language, and integrated to examine the overall effect of miR-140 on cartilage homeostasis. Down-regulation of miR-140 may have either detrimental or protective effects for cartilage, indicating that the role of miR-140 is complex. Studies of individual networks in isolation may therefore lead to different conclusions. This indicated the need to combine the five chosen individual networks involving miR-140 into an integrated model. This model suggests that the overall effect of miR-140 is to change the response to an IL-1 stimulus from a prolonged increase in matrix degrading enzymes to a pulse-like response so that cartilage degradation is temporary. Our current model can easily be modified and extended as more experimental data become available about the role of miR-140 in OA. In addition, networks of other microRNAs that are important in OA could be incorporated. A fully integrated model could not only aid our understanding of the mechanisms of microRNAs in ageing cartilage but could also provide a useful tool to investigate the effect of potential interventions to prevent cartilage loss.


Publication metadata

Author(s): Proctor CJ, Smith GR

Publication type: Article

Publication status: Published

Journal: PLoS ONE

Year: 2017

Volume: 12

Issue: 11

Online publication date: 02/11/2017

Acceptance date: 23/10/2017

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pone.0187568

DOI: 10.1371/journal.pone.0187568


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