AUTHOR=Wang Xiayi , Brouillette Marc J. , Ayati Bruce P. , Martin James A. TITLE=A Validated Model of the Pro- and Anti-Inflammatory Cytokine Balancing Act in Articular Cartilage Lesion Formation JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 3 - 2015 YEAR=2015 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2015.00025 DOI=10.3389/fbioe.2015.00025 ISSN=2296-4185 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.