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

PLoS One. 2017 Nov 2;12(11):e0187568. doi: 10.1371/journal.pone.0187568. eCollection 2017.


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.

MeSH terms

  • Computer Simulation*
  • Humans
  • Interleukin-1 / metabolism
  • Matrix Metalloproteinases / metabolism
  • MicroRNAs / physiology*
  • Osteoarthritis / genetics*
  • SOX9 Transcription Factor / metabolism
  • Systems Biology
  • Transforming Growth Factor beta / metabolism


  • Interleukin-1
  • MicroRNAs
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Transforming Growth Factor beta
  • Matrix Metalloproteinases