Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage

Baker, Michelle and Brook, Bindi S. and Owen, Markus R. (2017) Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage. Journal of Mathematical Biology . ISSN 1432-1416

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Abstract

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.

Item Type: Article
Keywords: Osteoarthritis, cytokine, modeling, simulation, non-linear dynamics
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Computer Science
University of Nottingham, UK > Faculty of Science > School of Mathematical Sciences
Identification Number: https://doi.org/10.1007/s00285-017-1104-y
Depositing User: Eprints, Support
Date Deposited: 08 Feb 2017 09:18
Last Modified: 24 Feb 2017 14:11
URI: http://eprints.nottingham.ac.uk/id/eprint/40411

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