Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis
This model is described in the article:
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 up-regulator 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.
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Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage.
- Baker M, Brook BS, Owen MR
- Journal of mathematical biology , 2/ 2017 , PubMed ID: 28213682
- School of Computer Science, University of Nottingham, Nottingham, UK. michelle.baker@nottingham.ac.uk.
- 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 up-regulator 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.
Submitter of this revision: Ahmad Zyoud
Modellers: Michelle Baker, Ahmad Zyoud
Metadata information
BioModels Database BIOMD0000000928
BioModels Database MODEL1704120000
isDescribedBy (1 statement)
hasProperty (2 statements)
isVersionOf (1 statement)
Connected external resources
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| Name | Description | Size | Actions |
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Model files |
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| Baker2017_Fig14..xml | SBML L3V1 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14 | 76.46 KB | Preview | Download |
Additional files |
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| Baker2017_Fig14.a_1.sedml | sed-ml L1V2 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14a-1 | 2.85 KB | Preview | Download |
| Baker2017_Fig14.a_2.sedml | sed-ml L1V2 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14a-2 | 2.83 KB | Preview | Download |
| Baker2017_Fig14.a_3.sedml | sed-ml L1V2 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14a-3 | 2.84 KB | Preview | Download |
| Baker2017_Fig14.b_1.sedml | sed-ml L1V2 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14b-1 | 2.84 KB | Preview | Download |
| Baker2017_Fig14.b_2.sedml | sed-ml L1V2 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14b-2 | 2.84 KB | Preview | Download |
| Baker2017_Fig14.cps | COPASI version 4.27 (Build 217) representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Curated-fig14 | 101.06 KB | Preview | Download |
| MODEL1704120000-biopax2.owl | Auto-generated BioPAX (Level 2) | 15.36 KB | Preview | Download |
| MODEL1704120000-biopax3.owl | Auto-generated BioPAX (Level 3) | 27.06 KB | Preview | Download |
| MODEL1704120000.m | Auto-generated Octave file | 4.95 KB | Preview | Download |
| MODEL1704120000.png | Auto-generated Reaction graph (PNG) | 79.56 KB | Preview | Download |
| MODEL1704120000.sci | Auto-generated Scilab file | 380.00 Bytes | Preview | Download |
| MODEL1704120000.svg | Auto-generated Reaction graph (SVG) | 23.57 KB | Preview | Download |
| MODEL1704120000.vcml | Auto-generated VCML file | 24.53 KB | Preview | Download |
| MODEL1704120000.xpp | Auto-generated XPP file | 3.00 KB | Preview | Download |
| MODEL1704120000_url.xml | SBML L3V1 representation of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis_Original | 19.71 KB | Preview | Download |
| MODEL1704120000_urn.xml | Auto-generated SBML file with URNs | 19.71 KB | Preview | Download |
- Model originally submitted by : Michelle Baker
- Submitted: Apr 12, 2017 10:02:35 AM
- Last Modified: Apr 2, 2020 5:32:03 PM
Revisions
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Version: 4
- Submitted on: Apr 2, 2020 5:32:03 PM
- Submitted by: Ahmad Zyoud
- With comment: Automatically added model identifier BIOMD0000000928
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Version: 2
- Submitted on: Jun 27, 2017 12:58:58 PM
- Submitted by: Michelle Baker
- With comment: Current version of Baker2017 - The role of cytokines, MMPs and fibronectin fragments osteoarthritis
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Version: 1
- Submitted on: Apr 12, 2017 10:02:35 AM
- Submitted by: Michelle Baker
- With comment: Original import of OAModelODE translated by MOCCASIN
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| solution0 Cytokine ; Inflammation |
0.18 mol |
| solution3 D-threo-Aldono-1,5-lactone |
0.75 mol |
| solution1 Cytokine ; Anti-inflammatory |
5.0 mol |
| solution2 Matrix Metalloproteinase |
0.55 mol |
| Reactions | Rate | Parameters |
|---|---|---|
| solution0 + solution1 => solution0 + solution1 | compartmentOne*1/(1+solution1^2)*Ppp/(1+solution0^2)*solution0^2/compartmentOne | Ppp = 10.0 |
| solution1 + solution3 => solution0 + solution1 + solution3 | compartmentOne*1/(1+solution1^2)*Pfp/(1+solution3^2)*solution3^2/compartmentOne | Pfp = 10.0 |
| solution1 => solution0 + solution1 | compartmentOne*Pbp/(1+solution1^2)/compartmentOne | Pbp = 0.01 |
| solution3 => solution1 + solution3 | compartmentOne*Afp*1/(Afh^2+solution3^2)*solution3^2/compartmentOne | Afh = 1.0; Afp = 10.0 |
| solution2 => | compartmentOne*Gamma_m*solution2/compartmentOne | Gamma_m = 1.0 |
| solution3 => | compartmentOne*Gamma_f*solution3/compartmentOne | Gamma_f = 1.0 |
| solution0 => solution0 + solution2 | compartmentOne*Mpp*1/(Mph^2+solution0^2)*solution0^2/compartmentOne | Mph = 1.0; Mpp = 10.0 |
(added: 02 Apr 2020, 17:31:45, updated: 02 Apr 2020, 17:31:45)