Using mouse models to investigate the pathophysiology, treatment, and prevention of post‐traumatic osteoarthritis

Abstract

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.

Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint

“…We demonstrate that higher mechanical impact over a longer time scale results in distinct molecular changes characteristic of PTOA as have been defined elsewhere31. ACL tear, one of the primary outcomes of loading, instigated many, if not all, of the subsequent events (except for primary cartilage injury and chondrocyte apoptosis).…”

Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis

“…Male C57BL/6J mice were purchased from Jackson Laboratories and were housed individually in micro-isolator cages on a 12 hour light/dark cycle. Male mice were used in this study due to a faster and more temporally predictable progression of degeneration that has been documented in models of PTOA [22]. Mice had ad libitum access to standard chow and fresh water, and were supplemented with hCol1 of bovine origin and a mean molecular weight of 2000 Da (Peptan ® B2000, Rousselot) using a method previously described to deliver daily doses of estradiol [23].…”

Pirfenidone reduces subchondral bone loss and fibrosis after murine knee cartilage injury

“…Post-traumatic OA is widely studied in clinical and animal model research to describe pathological remodeling in joint tissues after different types of injuries. 45,46 The severe murine cartilage injury used here had shown fibrotic, chondrogenic, and bone remodeling responses. 42 Toward efforts to identify novel therapeutic targets for different cellular response networks, we have here examined efficacy of the anti-fibrotic and anti-inflammatory drug PFD during the post-injury joint tissue regeneration response.…”

“…Post-traumatic OA is widely studied in clinical and animal model research to describe pathological remodeling in joint tissues after different types of injuries 45; 46 . The severe murine cartilage injury used here had shown fibrotic, chondrogenic, and bone remodeling responses 42 .…”