BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002.xpphttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002.mhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL1705170002?filename=MODEL1705170002.pngprimaryOK200Carole ProctorNon-curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/MODEL170517000229095952falseBioModelsSBMLModelsProctor2017 Role of microRNAs in osteoarthritis (miR140 IL1 incoherent feed forward)2017MODEL1705170002Carole J Proctor, Graham R SmithCarole J Proctor29095952, 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.. 11, 12. Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, United Kingdom.carole.proctor@ncl.ac.ukNewcastle UniversityThe 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.Computer simulation models as a tool to investigate the role of microRNAs in osteoarthritis.Proctor Carole J CJ, Smith Graham R GRpri miRNA, RNA, miRNAs, Small Temporal, Arthritides, Micro, Arthritis, Temporal RNA, stRNA, Degenerative Arthritides, osteoarthrosis, Small Temporal RNA, OA, Primary MicroRNA, Primary, miRNA, Primary miRNA, hypertrophic arthritis, pri-miRNA, feed., Concept, Small, degenerative joint disease, Osteoarthrosis Deformans, Role Concept, Micro RNA, Roles, osteoarthrosis and allied disorder, Degenerative, Osteoarthritides, Degenerative joint disease, Role Concepts, IL1, IL1-ALPHA, Role, Arthrosis, Concepts, IL1F1, MicroRNA, Arthroses, pre-miRNA, Osteoarthrosis, pre miRNA, Degenerative Arthritis, Osteoarthritis, Osteoarthroses, degenerative arthritis, IL-1Abiochemical pathways, extent, single-organism catabolic process, multicellular organismal catabolic process, SMAD family member 3, ccd, Materials, Public Sectors, Arthritides, HSN1E, determination, Languages, bar, Pb, Epidermal Cell Derived Thymocyte-Activating Factor, IDOL, XenMLP, Downregulation, mAb2A, Small, Readability, Donor Artificial Insemination, IL-1, anon-WO0134654.19, Macrophage Cell Factor, DmelCG4637, Anniversary, Cbfa1, Roles, osteoarthrosis and allied disorder, Osteoarthritides, HsT17436, cartilages, responsivity, CDA2, Xmad3, Concepts, madh3-A, cellular degradation, Mir, MIR, Public Enterprise, Osteoarthritis, Osteoarthroses, degenerative arthritis, Donor Artificial, Miranda, MADH3, hSMAD3, Su(var)3-103, Small Temporal, portion of cartilage tissue, enzymes, Arthritis, catabolism, Public Domains, purification, mir, cartilage tissue, miRNA, Primary miRNA, pri-miRNA, Computational, aml3, il1b-A, isolation and purification, Dedications, Degenerative joint disease, Role Concepts, Mothers against DPP homolog 3, biotransformation, Arthroses, In silico, Event, CXXC finger protein 9, Idol, Pebp2a1, cartilaginous tissue, T Helper Factor, 9430057C20Rik, ccd1, CBF-alpha-1, OSF-2, plomo, completeness, 6.3.2.-, AML3, acid, Blei, Small Temporal RNA, CLCD, plomb, 82Pb, Computer Simulations, Su-var(3)103, results, CG4637, CG12249, Literatures, Special Events, Role Concept, Receptor Down-Regulation, Public Domain, bar3, Role, Domains, IL1F1, XSmad3, Heterologous Insemination, Genetic Materials, IL1F2, secretion, Nucl, PEBP2aA, pre-miRNA, Osteoarthrosis, Genetic Material, Domain, hMAD-3, pri miRNA, Lymphocyte Activating Factor, Acid, ADCADN, miRNAs, Special Event, JIL1, l(3)neo56, Jil1, breakdown, l(3)neo57, Dialects, UNQ203/PRO229, Micro, Modeling, acide, DNA (cytosine-5-)-methyltransferase 1, Mira, Degenerative Arthritides, osteoarthrosis, mad3, CCD1, Computerized Model, acids, mMad3, Inducible degrader of the LDL-receptor, INSDC_feature:gene, acido, experimental procedures, Artificial Insemination, HSPC193, Sector, cartilage, Degenerative, Material, JIL, IL1-ALPHA, MIRA, Biocatalyst, MicroRNA, Cistron, pebp2aa1, D0Nds28, hg, HH, LDS1C, B530004O11Rik, Sectors, experimental, Su(var)3-1, JV15-2, Biocatalysts, stRNA, pebp2a1, Gene, In silico Modeling, Jil-1, Copyrights, Computer, interleukin-1 receptor ligand, Special, AID, chondrogenic tissue, cellular catabolism, Aid, Hh, Aim, AIM, Mad3, PEA2aA, IL1-BETA, D1Nds28, isolation, SMAD 3, anon-WO0118547.379, Computerized Models, Models, Enterprises, Cartilages, IL-1B, IL-1A, Pulses, aid, Smad 3, Insemination, DNMT1, study, reactivity, pebp2aa, osf2, methods, MONDOA, Genetic, DNMT1_HUMAN, breakdown of chemical, In silico Models, experimental section, Mrt, Interleukin I, Events, Interleukin 1, Public Enterprises, API6, degenerative joint disease, MSK, Su-var(3)1, Enzyme, Abstract, Myosin regulatory light chain-interacting protein, MAD homolog 3, Pebpa2a, CG6297, AU022421, regulation of cartilage homeostasis, bar-3, pebp2a2, HEL-S-284, Computer Model, lead, IL1, Smad3, HIGM2, bHLHe36, Cbfa-1, Model, Enterprise, In silico Model, Saeure, pre miRNA, Heterologous, DNA MTase HsaI, DNA (cytosine-5)-methyltransferase 1, cellular breakdown, RNA, l(3)hh, data, 2Ab17, degradation, Myosin regulatory light chain interacting protein, LS3, DNMT, Madh3, In silico Simulation, enzyme activity, Primary, Computational Modelling, MCMT, Cistrons, LDS3, pea2aa, Down Regulation, Concept, Computerized, Human Donor, Simulations, Anniversaries, AW228700, Osteoarthrosis Deformans, Down-Regulation, Micro RNA, Public, Computer Models, Down-Regulation (Physiology), DNA methyltransferase HsaI, chemical analysis, feed, DmelCG12249, Donor, Osf2, OSF2, cbfa1, DmelCG6297, Data Base, breakdown of molecule, CXXC9, Artificial, C23, Cbf, CT-2, biodegradation, Temporal RNA, Arp2, Saeuren, ARP2, plumbum, OA, Primary MicroRNA, Understanding, CBFA1, Dialect, negative regulation of cartilage homeostasis, Computational Modeling, hypertrophic arthritis, Modelling, CXXC-type zinc finger protein 9, ageing, breakdown of substance, CCD, Epidermal Cell Derived Thymocyte Activating Factor, anon-WO0182946.19, Arthrosis, Simulation, Public., assay, positive regulation of cartilage homeostasis, Receptor, Lymphocyte-Activating Factor, response, Degenerative Arthritis, CLEC2C, m.HsaIRNA, Arthritides, degenerative arthritis., stRNA, In silico Simulation, Small Temporal RNA, In silico Modeling, Primary, Computer, Computational Modelling, Computer Simulations, Computerized, Concept, Simulations, Small, Osteoarthrosis Deformans, Role Concept, Micro RNA, Roles, osteoarthrosis and allied disorder, Computer Models, Osteoarthritides, Role, Concepts, Computerized Models, pre-miRNA, Osteoarthrosis, Models, Osteoarthritis, Osteoarthroses, pri miRNA, miRNAs, Small Temporal, Micro, Arthritis, Temporal RNA, Modeling, In silico Models, Degenerative Arthritides, osteoarthrosis, OA, Computerized Model, Primary MicroRNA, Computational Modeling, miRNA, Primary miRNA, Modelling, hypertrophic arthritis, pri-miRNA, Computational, degenerative joint disease, Degenerative, Computer Model, Degenerative joint disease, Role Concepts, Arthrosis, MicroRNA, Simulation, Arthroses, Model, In silico, In silico Model, pre miRNA, Degenerative Arthritisbiochemical pathways, Networks, single-organism catabolic process, multicellular organismal catabolic process, SMAD family member 3, ccd, Arthritides, HSN1E, determination, Languages, cartilaginous tissue., bar, Pb, Epidermal Cell Derived Thymocyte-Activating Factor, sci, IDOL, XenMLP, Downregulation, mAb2A, Small, Readability, Donor Artificial Insemination, IL-1, anon-WO0134654.19, Macrophage Cell Factor, DmelCG4637, Cbfa1, Roles, osteoarthrosis and allied disorder, Circuit, Osteoarthritides, HsT17436, cartilages, responsivity, CDA2, Transcriptional Networks, Xmad3, HOW, How, Concepts, madh3-A, cellular degradation, Mir, MIR, protective, l(3)j5D5, IKKg, Osteoarthritis, Osteoarthroses, degenerative arthritis, KEY, Key, Donor Artificial, 24B, Miranda, MADH3, Transcriptional, hSMAD3, Su(var)3-103, Small Temporal, portion of cartilage tissue, enzymes, Arthritis, Biology, catabolism, stru, l(3)S053606, mir, cartilage tissue, miRNA, Primary miRNA, CG10293, pri-miRNA, aml3, il1b-A, l(3)j5B5, Degenerative joint disease, Role Concepts, Gene Network, Mothers against DPP homolog 3, biotransformation, Arthroses, CXXC finger protein 9, Idol, Pebp2a1, cartilaginous tissue, T Helper Factor, 9430057C20Rik, ccd1, 0904/17, CBF-alpha-1, OSF-2, plomo, 6.3.2.-, AML3, Blei, Small Temporal RNA, CLCD, plomb, 82Pb, Su-var(3)103, results, CG4637, CG12249, Literatures, DmIKKgamma, Role Concept, Receptor Down-Regulation, SZ1, dIKK, bar3, Kenny, Role, XSmad3, Heterologous Insemination, IL1F2, secretion, PEBP2aA, pre-miRNA, Osteoarthrosis, hMAD-3, pri miRNA, Lymphocyte Activating Factor, ADCADN, miRNAs, JIL1, l(3)neo56, Jil1, breakdown, l(3)neo57, Gene Circuit, Dialects, UNQ203/PRO229, Micro, DNA (cytosine-5-)-methyltransferase 1, decrease in risk, Mira, Degenerative Arthritides, osteoarthrosis, mad3, IKK-gamma, CCD1, mMad3, Inducible degrader of the LDL-receptor, Artificial Insemination, HSPC193, DmelCG16910, cartilage, Gene Modules, Regulatory Networks, Degenerative, JIL, MIRA, Biocatalyst, anon-EST:Liang-2.39, MicroRNA, pebp2aa1, hg, HH, LDS1C, Modules, Gene Regulatory, Su(var)3-1, JV15-2, Biocatalysts, P62, stRNA, pebp2a1, Gene, Jil-1, Network, interleukin-1 receptor ligand, AID, dIKK-gamma, chondrogenic tissue, cellular catabolism, Aid, Hh, Aim, AIM, Mad3, PEA2aA, IL1-BETA, DmIKK-gamma, SMAD 3, anon-WO0118547.379, Transcriptional Network, Gene Regulatory Network, dmIKKgamma, IKK[[gamma]], Module, Cartilages, IL-1B, Pulses, aid, Smad 3, Insemination, DNMT1, study, reactivity, pebp2aa, Regulatory Network, osf2, Circuits, l(3)s2612, MONDOA, DNMT1_HUMAN, breakdown of chemical, Mrt, Interleukin I, Interleukin 1, API6, degenerative joint disease, MSK, Su-var(3)1, Enzyme, Myosin regulatory light chain-interacting protein, MAD homolog 3, IKK, Pebpa2a, CG6297, AU022421, regulation of cartilage homeostasis, bar-3, pebp2a2, HEL-S-284, lead, DmelCG10293, Smad3, HIGM2, bHLHe36, Cbfa-1, pre miRNA, Heterologous, DNA MTase HsaI, DNA (cytosine-5)-methyltransferase 1, cellular breakdown, RNA, l(3)hh, data, 2Ab17, degradation, Myosin regulatory light chain interacting protein, clone 2.39, LS3, DNMT, Madh3, enzyme activity, Primary, MCMT, qkr, l(3)S090417, LDS3, pea2aa, Gene Circuits, Down Regulation, Concept, Human Donor, AW228700, IKKgamma, Osteoarthrosis Deformans, Down-Regulation, Micro RNA, Down-Regulation (Physiology), DNA methyltransferase HsaI, KH93F, chemical analysis, Systems, DmelCG12249, Donor, Osf2, OSF2, cbfa1, DmelCG6297, breakdown of molecule, who, CXXC9, Artificial, Cbf, CT-2, biodegradation, Gene Module, Temporal RNA, Dmikkgamma, Arp2, ARP2, plumbum, OA, Primary MicroRNA, Who/How, Understanding, CBFA1, Dialect, negative regulation of cartilage homeostasis, hypertrophic arthritis, CG16910, CXXC-type zinc finger protein 9, breakdown of substance, CCD, Epidermal Cell Derived Thymocyte Activating Factor, anon-WO0182946.19, Gene Networks, Arthrosis, qkr[93F], assay, positive regulation of cartilage homeostasis, Receptor, Lymphocyte-Activating Factor, response, Degenerative Arthritis, CLEC2C, m.HsaIfalseProctor2017- Role of microRNAs in osteoarthritis (miR140-IL1 incoherent feed forward) Proctor2017- Role of microRNAs in osteoarthritis (miR140-IL1 incoherent feed forward) This model is described in the article: Computer simulation models as a tool to investigate the role of microRNAs in osteoarthritis. Proctor CJ, Smith GR. PLoS ONE 2017; 12(11): e0187568 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: MODEL1705170002. 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. 2017-11-062017-05-17MODEL170517000229095952