title: 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.
  
  
  CONCLUSIONS
  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 1, while the second case has parameter values as in Table 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.
  
  
  CONCLUSIONS
  The mathematical model presented herein suggests that not only are anti-inflammatory cytokines, 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.
authors.affiliation: Department of Mathematics/Program in Applied Mathematical and Computational Sciences, University of Iowa, Iowa City, IA, USA. jason-graham@uiowa.edu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Graham
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Ayati
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.forename: Prem S
authors.initials: PS
authors.lastname: Ramakrishnan
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
mesh_terms: D017209:Apoptosis; D001692:Biological Transport; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D019295:Computational Biology; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008962:Models, Theoretical; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D025941:Protein Interaction Mapping; D017382:Reactive Oxygen Species / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D017467:Receptors, Erythropoietin; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin