Dataset Information

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

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.

SUBMITTER: Proctor CJ

PROVIDER: S-EPMC5695613 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Proctor Carole J CJ Smith Graham R GR

PloS one 20171102 11

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 ...[more]

PMID: 29095952

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Project description:This article describes simulation research based on the Hamiltonian theory of gene-based altruism. It investigates the origin of semipermanent breeding bonds during hominin evolution. The research framework is based on a biologically detailed, ecologically situated, multi-agent microsimulation of emergent sociality. The research question tested is whether semipermanent breeding bonds (an emergent homoplastic social construct) might emerge among primate-like agents as the consequence of a mutation capable of supporting involuntary prosocial behavior. The research protocol compared several, single independent-variable longitudinal studies wherein hundreds of generations of autonomous, initially promiscuous, biologically detailed, hominin-like artificial life software agents were born, allowed to forage, reproduce, and die during experimental intervals lasting several simulated millennia. The temporal setting of the experiment was roughly contemporaneous with, or slightly after the time of, the Pan-Homo split. The simulation investigated what would happen if, within a population, a single gene for prosocial behavior (the independent variable in the experiment) was either switched on or switched-off. The null hypothesis predicted that, if the gene was switched off, then semipermanent breeding bonds (the dependent variable) would nonetheless emerge within the population. The results of the simulation rejected this null hypothesis, by showing that semipermanent breeding bonds would reliably emerge among the experimental populations but not among the control groups. Moreover, it was found that, across all experimental settings having constrained population numbers, the portion of each population having no prosocial trait would die out early, whereas the portion with the prosocial trait would survive. Large control populations had no discernible loss. The results of this research imply that, during the early stages of hominin evolution, there might have been a set of initially gene-based, altruistic excess forage-sharing social traits that contributed to the onset of morphological and additional complex social changes characteristic of this group. This work also demonstrates that modern computational technologies can extend our ability to test 'what if' hypotheses appropriate to the study of early hominin evolution.

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Dataset Information

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

Publications

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

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