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Logo of bioldirectBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleBiology DirectJournal Front Page
 
Biol Direct. 2012; 7: 9.
Published online 2012 February 21. doi:  10.1186/1745-6150-7-9
PMCID: PMC3356234

Reaction-Diffusion-Delay Model for EPO/TNF-α Interaction in articular cartilage lesion abatement

Abstract

Background

Injuries to articular cartilage result in the development of lesions that form on the surface of the cartilage. Such lesions are associated with articular cartilage degeneration and osteoarthritis. The typical injury response often causes collateral damage, primarily an effect of inflammation, which results in the spread of lesions beyond the region where the initial injury occurs.

Results and discussion

We present a minimal mathematical model based on known mechanisms to investigate the spread and abatement of such lesions. The first case corresponds to the parameter values listed in Table Table1,1, while the second case has parameter values as in Table Table2.2. In particular we represent the "balancing act" between pro-inflammatory and anti-inflammatory cytokines that is hypothesized to be a principal mechanism in the expansion properties of cartilage damage during the typical injury response. We present preliminary results of in vitro studies that confirm the anti-inflammatory activities of the cytokine erythropoietin (EPO). We assume that the diffusion of cytokines determine the spatial behavior of injury response and lesion expansion so that a reaction diffusion system involving chemical species and chondrocyte cell state population densities is a natural way to represent cartilage injury response. We present computational results using the mathematical model showing that our representation is successful in capturing much of the interesting spatial behavior of injury associated lesion development and abatement in articular cartilage. Further, we discuss the use of this model to study the possibility of using EPO as a therapy for reducing the amount of inflammation induced collateral damage to cartilage during the typical injury response.

Table 1

Model Parameter Values for Results in Figure 5

Table of Parameter Values Corresponding to Simulations in Figure 5
ParameterValueUnitsReason

DR0.1cm2dayDetermined from []

DM0.05cm2dayDetermined from []

DF0.05cm2dayDetermined from []

DP0.005cm2dayDetermined from []

δR0.011dayApproximated

δM0.61dayApproximated

δF0.61dayApproximated

δP0.00871dayApproximated

δU0.00011dayApproximated

σR0.0001micromolarcm2daycellsApproximated

σM0.00001micromolarcm2daycellsApproximated

σF0.0001micromolarcm2daycellsApproximated

σP0micromolarcm2daycellsCase with no anti-inflammatory response

Λ10micromolarApproximated

λR10micromolarApproximated

λM10micromolarApproximated

λF10micromolarApproximated

λP10micromolarApproximated

α01dayCase with no anti-inflammatory response

β11001dayApproximated

Β2501dayApproximated

γ101dayApproximated

ν0.51dayApproximated

μSA11dayApproximated

μDN0.51dayApproximated

τ10.5daysTaken from []

τ21daysTaken from []

Table 2

Model Parameter Values for Results in Figure 6

Table of Parameter Values Corresponding to Simulations in Figure 6
ParameterValueUnitsReason

DR0.1cm2dayDetermined from []

DM0.05cm2dayDetermined from []

DF0.05cm2dayDetermined from []

DP0.005cm2dayDetermined from []

δR0.011dayApproximated

δM0.61dayApproximated

δF0.61dayApproximated

δP0.00871dayApproximated

δU0.00011dayApproximated

σR0.0001micromolarcm2daycellsApproximated

σM0.00001micromolarcm2daycellsApproximated

σF0.0001micromolarcm2daycellsApproximated

σP0.001micromolarcm2daycellsApproximated

Λ10micromolarApproximated

λR10micromolarApproximated

λM10micromolarApproximated

λF10micromolarApproximated

λP10micromolarApproximated

α101dayApproximated

β11001dayApproximated

β2501dayApproximated

γ101dayApproximated

ν0.51dayApproximated

μSA11dayApproximated

μDN0.51dayApproximated

τ10.5daysTaken from []

τ21daysTaken from []

Conclusions

The mathematical model presented herein suggests that not only are anti-inflammatory cy-tokines, such as EPO necessary to prevent chondrocytes signaled by pro-inflammatory cytokines from entering apoptosis, they may also influence how chondrocytes respond to signaling by pro-inflammatory cytokines.

Reviewers

This paper has been reviewed by Yang Kuang, James Faeder and Anna Marciniak-Czochra.


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