ANIMO for modelling cell homeostasis
When cartilage tissue is damaged different signals are generated, causing inflammation and subsequent cartilage degeneration. These signals counteract and may overrule the intrinsic repair response of cartilage. The complexity of the integrating signals severely constrains a complete and quantitative analysis of the precise signals that dictate cartilage maintenance.
To obtain insight into the function of this complex network we generated a dynamic computational model of chondrocytes, the Executable CHOndrocyte or ECHO. In ECHO cell fates corresponding to osteoarthritis as well as healthy chondrocytes can be investigated. We use ECHO to predict potential targets for switching from an OA-like chondrocyte to a healthy articular chondrocyte. Using ECHO, we analyze the most influential pathways and performed in silico experiments to obtain insight into the molecular mechanisms of cartilage development and disease. ECHO’s predictions are validated by biochemical (qPCR, IHC, IF) and biophysical techniques (FRAP and FRET).
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