Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage
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 concen...
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| Format: | Article |
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Springer Verlag
2017
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| Online Access: | https://eprints.nottingham.ac.uk/40411/ |
| _version_ | 1848796049836081152 |
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| author | Baker, Michelle Brook, Bindi S. Owen, Markus R. |
| author_facet | Baker, Michelle Brook, Bindi S. Owen, Markus R. |
| author_sort | Baker, Michelle |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:41:48Z |
| format | Article |
| id | nottingham-40411 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:41:48Z |
| publishDate | 2017 |
| publisher | Springer Verlag |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-404112020-05-04T18:34:18Z https://eprints.nottingham.ac.uk/40411/ Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage Baker, Michelle Brook, Bindi S. Owen, Markus R. 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. Springer Verlag 2017-02-17 Article PeerReviewed Baker, Michelle, 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 Osteoarthritis cytokine modeling simulation non-linear dynamics http://link.springer.com/article/10.1007%2Fs00285-017-1104-y doi:10.1007/s00285-017-1104-y doi:10.1007/s00285-017-1104-y |
| spellingShingle | Osteoarthritis cytokine modeling simulation non-linear dynamics Baker, Michelle Brook, Bindi S. Owen, Markus R. Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage |
| title | Mathematical modelling of cytokines, MMPs and
fibronectin fragments in osteoarthritic cartilage |
| title_full | Mathematical modelling of cytokines, MMPs and
fibronectin fragments in osteoarthritic cartilage |
| title_fullStr | Mathematical modelling of cytokines, MMPs and
fibronectin fragments in osteoarthritic cartilage |
| title_full_unstemmed | Mathematical modelling of cytokines, MMPs and
fibronectin fragments in osteoarthritic cartilage |
| title_short | Mathematical modelling of cytokines, MMPs and
fibronectin fragments in osteoarthritic cartilage |
| title_sort | mathematical modelling of cytokines, mmps and
fibronectin fragments in osteoarthritic cartilage |
| topic | Osteoarthritis cytokine modeling simulation non-linear dynamics |
| url | https://eprints.nottingham.ac.uk/40411/ https://eprints.nottingham.ac.uk/40411/ https://eprints.nottingham.ac.uk/40411/ |