Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage
Baker, Michelle; Brook, Bindi S.; Owen, Markus R.
Bindi S. Brook
Markus R. Owen
Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of cell signalling proteins, present in raised concentrations in OA joints, can be classified into pro-inflammatory and anti-inflammatory groups. They mediate cartilage degradation through several mechanisms, primarily the up-regulation of matrix metalloproteinases (MMPs), a group of collagen-degrading enzymes. In this paper we show that the interactions of cytokines within cartilage have a crucial role to play in OA progression and treatment. We develop a four-variable ordinary differential equation model for the interactions between pro- and anti-inflammatory cytokines, MMPs and fibronectin fragments (Fn-fs), a by-product of cartilage degradation and upregulator of cytokines. We show that the model has four classes of dynamic behaviour: homoeostasis, bistable inflammation, tristable inflammation and persistent inflammation. We show that positive and negative feedbacks controlling cytokine production rates can determine either a pre-disposition to OA or initiation of OA. Further, we show that manipulation of cytokine, MMP and Fn-fs levels can be used to treat OA, but we suggest that multiple treatment targets may be essential to halt or slow disease progression.
|Journal Article Type||Article|
|Journal||Journal of Mathematical Biology|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Baker, M., Brook, B. S., & Owen, M. R. (2017). Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage. Journal of Mathematical Biology, 75(4), 985-1024. https://doi.org/10.1007/s00285-017-1104-y|
|Keywords||Osteoarthritis, cytokine, modeling, simulation, non-lineardynamics|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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