Using mouse models to investigate the pathophysiology, treatment, and prevention of post-traumatic osteoarthritis.
Post-traumatic osteoarthritis (PTOA) is defined by its development after joint injury. Factors contributing to the risk of PTOA occurring, the rate of progression, and degree of associated disability in any individual, remain incompletely understood. What constitutes an "OA-inducing injury" is not defined. In line with advances in the traumatic brain injury field, we propose the scope of PTOA-inducing injuries be expanded to include not only those causing immediate structural damage and instability (Type I), but also those without initial instability/damage from moderate (Type II) or minor (Type III) loading severity. A review of the literature revealed this full spectrum of potential PTOA subtypes can be modeled in mice, with 27 Type I, 6 Type II, and 4 Type III models identified. Despite limitations due to cartilage anatomy, joint size, and bio-fluid availability, mice offer advantages as preclinical models to study PTOA, particularly genetically modified strains. Histopathology was the most common disease outcome, cartilage more frequently studied than bone or synovium, and meniscus and ligaments rarely evaluated. Other methods used to examine PTOA included gene expression, protein analysis, and imaging. Despite the major issues reported by patients being pain and biomechanical dysfunction, these were the least commonly measured outcomes in mouse models. Informative correlations of simultaneously measured disease outcomes in individual animals, was rarely done in any mouse PTOA model. This review has identified knowledge gaps that need to be addressed to increase understanding and improve prevention and management of PTOA. Preclinical mouse models play a critical role in these endeavors. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:424-439, 2017.
Murray Maxwell Biomechanics Laboratory, Institute of Bone and Joint Research, Level 10, Kolling Institute B6, Northern Sydney Local Health District, Sydney Medical School Northern, University of Sydney, The Royal North Shore Hospital, St. Leonards, New South Wales, 2065, Australia.|Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute, Northern Sydney Local Health District, Sydney Medical School Northern, University of Sydney, St. Leonards, New South Wales, 2065, Australia.
Carina L
CL
Blaker
Murray Maxwell Biomechanics Laboratory, Institute of Bone and Joint Research, Level 10, Kolling Institute B6, Northern Sydney Local Health District, Sydney Medical School Northern, University of Sydney, The Royal North Shore Hospital, St. Leonards, New South Wales, 2065, Australia.
Elizabeth C
EC
Clarke
Raymond Purves Bone and Joint Research Laboratories, Institute of Bone and Joint Research, Kolling Institute, Northern Sydney Local Health District, Sydney Medical School Northern, University of Sydney, St. Leonards, New South Wales, 2065, Australia.
Christopher B
CB
Little
D000818:Animals; D004195:Disease Models, Animal; D007596:Joints / Q000293:injuries*; D051379:Mice; D010003:Osteoarthritis / Q000209:etiology*; D014947:Wounds and Injuries / Q000150:complications*
disease model; mouse; post-traumatic osteoarthritis