Hui2016 - Age-related changes in articular cartilage

  public model
Model Identifier
BIOMD0000000560
Short description
Hui2014 - Age-related changes in articular cartilage

This model is described in the article:

Wang Hui1, David A Young1, Andrew D Rowan1, Xin Xu2, Tim E Cawston1, Carole J Proctor1,3
Annals of the Rheumatic Diseases

Abstract:

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.

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 CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Oxidative changes and signalling pathways are pivotal in initiating age-related changes in articular cartilage.
  • Hui W, Young DA, Rowan AD, Xu X, Cawston TE, Proctor CJ
  • Annals of the rheumatic diseases , 2/ 2016 , Volume 75 , pages: 449-458 , PubMed ID: 25475114
  • MRC/Arthritis Research UK Centre for Musculoskeletal Ageing (CIMA), Musculoskeletal Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
  • To use a computational approach to investigate the cellular and extracellular matrix changes that occur with age in the knee joints of mice.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.A progressive loss of cartilage matrix occurred with age. Nitrotyrosine, MMP-13 and activin receptor-like kinase-1 (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-β 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.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.
Contributors
Krishna Kumar Tiwari, Carole Proctor

Metadata information

is
BioModels Database MODEL1402200004
BioModels Database BIOMD0000000560
isDescribedBy
PubMed 25475114
hasTaxon
Taxonomy Mus musculus
hasProperty
Human Disease Ontology osteoarthritis
occursIn

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000560_url.xml SBML L2V4 representation of Hui2014 - Age-related changes in articular cartilage 174.88 KB Preview | Download

Additional files

BIOMD0000000560.xpp Auto-generated XPP file 30.82 KB Preview | Download
BIOMD0000000560.vcml Auto-generated VCML file 897.00 Bytes Preview | Download
BIOMD0000000560.png Auto-generated Reaction graph (PNG) 3.91 MB Preview | Download
BIOMD0000000560.svg Auto-generated Reaction graph (SVG) 413.02 KB Preview | Download
BIOMD0000000560-biopax3.owl Auto-generated BioPAX (Level 3) 346.89 KB Preview | Download
BIOMD0000000560.sci Auto-generated Scilab file 27.02 KB Preview | Download
BIOMD0000000560-biopax2.owl Auto-generated BioPAX (Level 2) 196.80 KB Preview | Download
BIOMD0000000560.pdf Auto-generated PDF file 755.17 KB Preview | Download
BIOMD0000000560_urn.xml Auto-generated SBML file with URNs 172.78 KB Preview | Download
BIOMD0000000560.m Auto-generated Octave file 42.27 KB Preview | Download

  • Model originally submitted by : Carole Proctor
  • Submitted: Feb 20, 2014 1:27:41 PM
  • Last Modified: Sep 4, 2019 3:34:15 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Sep 4, 2019 3:34:15 PM
    • Submitted by: Krishna Kumar Tiwari
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Apr 8, 2016 6:51:50 PM
    • Submitted by: Carole Proctor
    • With comment: Current version of Hui2014 - Age-related changes in articular cartilage
  • Version: 1 public model Download this version
    • Submitted on: Feb 20, 2014 1:27:41 PM
    • Submitted by: Carole Proctor
    • With comment: Original import of BIOMD0000000560.xml.origin

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Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
Sox9_A => Sox9_A + AcanmRNA; Sox9_A ksynAcanmRNASox9A*Sox9_A ksynAcanmRNASox9A = 4.6E-6
AcanmRNA => Sink; AcanmRNA kdegAcanmRNA*AcanmRNA kdegAcanmRNA = 9.0E-6
AcanmRNA => AcanmRNA + Aggrecan; AcanmRNA ksynAggrecan*AcanmRNA ksynAggrecan = 1.0E-6
IL1 => IL1 + ADAMTS5; IL1 ksynADAMTS5*IL1 ksynADAMTS5 = 5.0E-4
Alk1_Alk5 => Alk1 + Alk5; Alk1_Alk5 krelAlk1Alk5*Alk1_Alk5 krelAlk1Alk5 = 0.01
Source => Alk1; Source ksynAlk1*Source ksynAlk1 = 5.0E-6
Tgfb_A + Alk1_Alk5 => Tgfb_Alk1_Alk5; Tgfb_A, Alk1_Alk5 kbinTgfbAlk1*Tgfb_A*Alk1_Alk5 kbinTgfbAlk1 = 2.0E-5
Tgfb_Alk1_Alk5 => Tgfb_A + Alk1_Alk5; Tgfb_Alk1_Alk5 krelTgfbAlk1*Tgfb_Alk1_Alk5 krelTgfbAlk1 = 1.0E-6
Source => Alk5; Source ksynAlk5*Source ksynAlk5 = 5.0E-6
Alk5 => Alk5_dimer; Alk5 kdimerAlk5*Alk5*(Alk5-1)*0.5 kdimerAlk5 = 2.0E-4
Smad1_P_Smad4 => Smad1_P + Smad4; Smad1_P_Smad4 krelSmad1Smad4*Smad1_P_Smad4 krelSmad1Smad4 = 0.0167
Smad2_P => Smad2; Smad2_P kdephosSmad2*Smad2_P kdephosSmad2 = 0.006
Tgfb_Alk5_dimer + Smad2 => Tgfb_Alk5_dimer + Smad2_P; Tgfb_Alk5_dimer, Smad2 kphosSmad2*Tgfb_Alk5_dimer*Smad2 kphosSmad2 = 4.0E-5
Alk5_dimer => Alk5; Alk5_dimer kdedimerAlk5*Alk5_dimer kdedimerAlk5 = 0.001
Tgfb_A + Alk5_dimer => Tgfb_Alk5_dimer; Tgfb_A, Alk5_dimer kbinTgfbAlk5*Tgfb_A*Alk5_dimer kbinTgfbAlk5 = 3.0E-5
Curator's comment:
(added: 05 Dec 2014, 17:00:19, updated: 05 Dec 2014, 17:00:19)
Figure 5C of the reference publication has been reproduced. One stochastic simulation was carried out using Copasi v4.14 (Build 89). In the paper, 500 stochastic simulations has been carried out and figure 5c is a randomly chosen simulation result.