Proctor2017- Role of microRNAs in osteoarthritis (Positive Feedforward Incoherent By MicroRNA)_1
This model is described in the article:
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-?B, 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.
This model is hosted on BioModels Database and identified by: MODEL1610100004.
To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
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.
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Computer simulation models as a tool to investigate the role of microRNAs in osteoarthritis.
- Proctor CJ, Smith GR
- PloS one , 1/ 2017 , Volume 12 , Issue 11 , pages: e0187568 , PubMed ID: 29095952
- Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom.
- 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.
Submitter of this revision: Mohammad Umer Sharif Shohan
Modellers: Carole Proctor, Mohammad Umer Sharif Shohan
Metadata information
Taxonomy Homo sapiens
Mathematical Modelling Ontology Ordinary differential equation model
is (1 statement)
hasProperty (2 statements)
isDescribedBy (2 statements)
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| proctor2017_model4.xml | SBML L2V4 representation of Proctor2017- Role of microRNAs in osteoarthritis (Positive Feedforward Incoherent By MicroRNA) | 26.26 KB | Preview | Download |
Additional files |
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| MODEL1610100004-biopax2.owl | Auto-generated BioPAX (Level 2) | 8.45 KB | Preview | Download |
| MODEL1610100004-biopax3.owl | Auto-generated BioPAX (Level 3) | 14.74 KB | Preview | Download |
| MODEL1610100004.m | Auto-generated Octave file | 3.92 KB | Preview | Download |
| MODEL1610100004.png | Auto-generated Reaction graph (PNG) | 24.18 KB | Preview | Download |
| MODEL1610100004.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
| MODEL1610100004.svg | Auto-generated Reaction graph (SVG) | 12.07 KB | Preview | Download |
| MODEL1610100004.vcml | Auto-generated VCML file | 15.96 KB | Preview | Download |
| MODEL1610100004.xpp | Auto-generated XPP file | 2.03 KB | Preview | Download |
| MODEL1610100004_url.xml | old xml file | 10.88 KB | Preview | Download |
| MODEL1610100004_urn.xml | Auto-generated SBML file with URNs | 10.46 KB | Preview | Download |
| Proctor2017_model4.cps | COPASI version 4.24 (Build 197) Role of microRNAs in osteoarthritis (Positive Feedforward Incoherent By MicroRNA) | 52.33 KB | Preview | Download |
| proctor2017_model4.sedml | SEDML L1V2 Role of microRNAs in osteoarthritis (Positive Feedforward Incoherent By MicroRNA) | 1.01 KB | Preview | Download |
- Model originally submitted by : Carole Proctor
- Submitted: Oct 10, 2016 4:21:45 PM
- Last Modified: Nov 14, 2019 10:53:44 AM
Revisions
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Version: 4
- Submitted on: Nov 14, 2019 10:53:44 AM
- Submitted by: Mohammad Umer Sharif Shohan
- With comment: Automatically added model identifier BIOMD0000000860
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Version: 3
- Submitted on: Nov 14, 2019 10:40:34 AM
- Submitted by: Mohammad Umer Sharif Shohan
- With comment: Curated and annotated
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Version: 2
- Submitted on: Nov 6, 2017 11:20:56 AM
- Submitted by: Carole Proctor
- With comment: Current version of MODEL1610100004
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Version: 1
- Submitted on: Oct 10, 2016 4:21:45 PM
- Submitted by: Carole Proctor
- With comment: Original import of MODEL1610100004
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| TF1 1,4-beta-D-Mannooligosaccharide |
0.0 item |
| Sink | 0.0 item |
| miR C25966 |
0.0 item |
| TF1target mRNA | 0.0 item |
| Reactions | Rate | Parameters |
|---|---|---|
| TF1 => TF1 + miR | cell*ksynMiR*TF1*cell/cell | ksynMiR = 2.0E-4 1/s |
| TF1target_mRNA + miR => Sink + miR | cell*kdegTF1targetmRNAbyMiR*TF1target_mRNA*cell*miR*cell/cell | kdegTF1targetmRNAbyMiR = 5.0E-5 1/ (mol *s) |
| miR => Sink | cell*kdegMiR*miR*cell/cell | kdegMiR = 4.0E-4 1/s |
| TF1 => TF1 + TF1target_mRNA | cell*ksynTF1targetmRNA*TF1*cell/cell | ksynTF1targetmRNA = 0.004 1/s |
| TF1target_mRNA => Sink | cell*kdegTF1targetmRNA*TF1target_mRNA*cell/cell | kdegTF1targetmRNA = 0.001 1/s |
(added: 14 Nov 2019, 10:49:52, updated: 14 Nov 2019, 10:49:52)