title: A validated model of the pro- and anti-inflammatory cytokine balancing act in articular cartilage lesion formation.
abstract: Traumatic injuries of articular cartilage result in the formation of a cartilage lesion and contribute to cartilage degeneration and the risk of osteoarthritis (OA). A better understanding of the framework for the formation of a cartilage lesion formation would be helpful in therapy development. Toward this end, we present an age and space-structured model of articular cartilage lesion formation after a single blunt impact. This model modifies the reaction-diffusion-delay models in Graham et al. (2012) (single impact) and Wang et al. (2014) (cyclic loading), focusing on the "balancing act" between pro- and anti-inflammatory cytokines. Age structure is introduced to replace the delay terms for cell transitions used in these earlier models; we find age structured models to be more flexible in representing the underlying biological system and more tractable computationally. Numerical results show a successful capture of chondrocyte behavior and chemical activities associated with the cartilage lesion after the initial injury; experimental validation of our computational results is presented. We anticipate that our in silico model of cartilage damage from a single blunt impact can be used to provide information that may not be easily obtained through in in vivo or in vitro studies.
authors: Program in Applied Mathematical and Computational Sciences, University of Iowa , Iowa City, IA , USA.
authors: Xiayi
authors: X
authors: Wang
authors: Department of Orthopaedics and Rehabilitation, University of Iowa , Iowa City, IA , USA ; Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA.
authors: Marc J
authors: MJ
authors: Brouillette
authors: Program in Applied Mathematical and Computational Sciences, University of Iowa , Iowa City, IA , USA ; Department of Orthopaedics and Rehabilitation, University of Iowa , Iowa City, IA , USA ; Department of Mathematics, University of Iowa , Iowa City, IA , USA.
authors: Bruce P
authors: BP
authors: Ayati
authors: Department of Orthopaedics and Rehabilitation, University of Iowa , Iowa City, IA , USA ; Department of Biomedical Engineering, University of Iowa , Iowa City, IA , USA.
authors: James A
authors: JA
authors: Martin
keywords: EPO; IL-6; articular cartilage; lesion formation and abatement; structured model