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

PloS One
C J Proctor, Graham R Smith

Abstract

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 abou...Continue Reading

References

Jul 23, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Sherri R DaviesLinda J Sandell
Jan 18, 2006·Bioinformatics·Colin S GillespieThomas B L Kirkwood
Jun 15, 2006·Molecular Systems Biology·Naama Geva-ZatorskyUri Alon
Oct 13, 2006·Bioinformatics·Stefan HoopsUrsula Kummer
May 19, 2007·Nature Reviews. Genetics·Uri Alon
Aug 19, 2008·BMC Systems Biology·Carole J Proctor, Douglas A Gray
Feb 17, 2009·The Journal of Biological Chemistry·Guannan WangFang Liu
Mar 11, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Natalia J Martinez, Albertha J M Walhout
Aug 12, 2009·Nature Biotechnology·Nicolas Le NovèreHiroaki Kitano
Dec 2, 2009·BMC Musculoskeletal Disorders·Ginette TardifJohanne Martel-Pelletier
Dec 2, 2009·The Journal of Cell Biology·Ellen BellonPrzemko Tylzanowski
May 15, 2010·Genes & Development·Shigeru MiyakiHiroshi Asahara
Jul 2, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Aixin Cheng, Paul G Genever
Aug 14, 2010·EMBO Reports·Simone Brabletz, Thomas Brabletz
Sep 3, 2010·Theory in Biosciences = Theorie in Den Biowissenschaften·Svetoslav NikolovOlaf Wolkenhauer
Mar 23, 2011·PLoS Computational Biology·Matteo OsellaMichele Caselle
Nov 5, 2011·Applied Biochemistry and Biotechnology·Yukio NakamuraJohn H Postlethwait
Jan 26, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Zu-Jian LiangBai-Dang Zhang
Feb 1, 2013·PloS One·Hye-Won KangAvner Friedman
Feb 5, 2013·Advances in Experimental Medicine and Biology·Julio VeraOlaf Wolkenhauer
May 15, 2013·Arthritis and Rheumatism·Linh T T LeIan M Clark
Aug 15, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Rui ZhangJianfeng Yao
Oct 2, 2013·Annual Review of Pathology·Gianpiero Di LevaCarlo M Croce
Dec 23, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Garyfallia PapaioannouTatsuya Kobayashi
Nov 22, 2015·Nucleic Acids Research·Chih-Hung ChouHsien-Da Huang
Dec 3, 2016·Nucleic Acids Research·Gautier KoscielnyIan Dunham
Mar 28, 2017·Journal of Cellular and Molecular Medicine·Jian WuNaizhou Guo

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