biostudies-otherUnknown75Lucian SmithAnnals of the rheumatic diseases449-458Mus musculushttps://www.ebi.ac.uk/biostudies/studies/MODEL1402200004biostudies-other25475114Krishna Kumar TiwariLucian SmithCarole ProctorfalseHui2016 - Age-related changes in articular cartilage<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <div class="dc:title">Hui2014 - Age-related changes in articularcartilage</div><div class="dc:bibliographicCitation"> <p>This model is described in the article:</p> <div class="bibo:title"> <a href="http://identifiers.org/doi/doi:%2010.1136/annrheumdis-2014-206295" title="Access to this publication">Oxidative changes and signalling pathways are pivotal in initiating age-related changes in articular cartilage</a> </div> <div class="bibo:authorList">Wang Hui1, David A Young1, Andrew D Rowan1, Xin Xu2, Tim E Cawston1, Carole J Proctor1,3</div> <div class="bibo:Journal">Annals of the Rheumatic Diseases</div> <p>Abstract:</p> <div class="bibo:abstract"> <p>Objective: To use a computational approach to investigate the cellular and extracellular matrix changes that occur with age in the knee joints of mice. Methods: Knee joints from an inbred C57/BL1/6 (ICRFa) mouse colony were harvested at 3–30?months of age. Sections were stained with H&E, Safranin-O, Picro-sirius red and antibodies to matrix metalloproteinase-13 (MMP-13), nitrotyrosine, LC-3B, Bcl-2, and cleaved type II collagen used for immunohistochemistry. Based on this and other data from the literature, a computer simulation model was built using the Systems Biology Markup Language using an iterative approach of data analysis and modelling. Individual parameters were subsequently altered to assess their effect on the model. Results: A progressive loss of cartilage matrix occurred with age. Nitrotyrosine, MMP-13 and anaplastic lymphoma kinase (ALK1) staining in cartilage increased with age with a concomitant decrease in LC-3B and Bcl-2. Stochastic simulations from the computational model showed a good agreement with these data, once transforming growth factor-? signalling via ALK1/ALK5 receptors was included. Oxidative stress and the interleukin 1 pathway were identified as key factors in driving the cartilage breakdown associated with ageing. Conclusions: A progressive loss of cartilage matrix and cellularity occurs with age. This is accompanied with increased levels of oxidative stress, apoptosis and MMP-13 and a decrease in chondrocyte autophagy. These changes explain the marked predisposition of joints to develop osteoarthritis with age. Computational modelling provides useful insights into the underlying mechanisms involved in age-related changes in musculoskeletal tissues.</p> </div></div><div class="dc:publisher"> <p>This model is hosted on <a href="http://www.ebi.ac.uk/biomodels/">BioModels Database</a> and identified by: <a href="http://identifiers.org/biomodels.db/BIOMD0000000560">BIOMD0000000560</a>.</p> <p>To cite BioModels Database, please use: <a href="http://identifiers.org/pubmed/20587024" title="Latest BioModels Database publication">BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models</a>.</p></div><div class="dc:license"> <p>To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to <a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0 Public Domain Dedication</a> for more information.</p></div></body> </notes>2014-02-20T00:00:00Z2025-07-15T10:01:00.985Z2025-03-29T17:54:45.211ZMODEL1402200004BIOMD000000056025475114PR:000037070CHEBI:26523GO:0005623GO:0005634GO:0016020GO:0065010GO:0008305GO:0051216GO:0001322GO:0005764PATO:0000070PATO:0001444DOID:839810090FMA:35175P01583Q14457Q16539Q13950Q15797P10415Q15109P36897P37023P16112Q9UNA0Q04206Q07812P45452O15105P48436P02458P08253P01137P42574Q15796Q13485P25963P00441