In humans, osteoarthritis (OA) develops either idiopathically and progresses slowly with age or secondarily to trauma and progresses rapidly. OA is associated with changes to all joint tissues including articular cartilage, subchondral bone, synovium, ligaments, and muscles. Clinically, OA-mediated joint damage results in reduced mobility, pain, and fatigue. While several disease modifying OA drugs are in various stages of development, none have yet been approved for human use. Concurrent research in humans as well as experimental animal models will be important for the discovery of new therapeutics. Since no single experimental model provides the complete picture of OA in humans, a variety of animals have served to advance OA research including mouse, rat, guinea pig, rabbit, dog, and horse. [1,2]
A broad range of rabbit OA models have been used extensively and continue to offer specific advantages over other models for OA research. The gross anatomy of the rabbit knee is very similar to that of humans. Moreover, the rabbit knee joint is large enough to enable the harvest of adequate volumes of tissue for histopathological analysis, a major limitation of smaller animal models. In adult humans, the growth plates in the long bones no longer retain the capacity for growth and are termed “closed.” This is also the case in skeletally-mature rabbits. By contrast, mouse and rat growth plates do not normally close completely and longitudinal bone growth can be reinitiated even in mature animals. This is a complicating issue for data interpretation and limits the translatability of research performed using mice and rats. [2]
Most often, skeletally-mature, male, NZW rabbits are used for OA studies in an attempt to ensure bone growth plate closure, reduce hormone fluctuation, and control for potential inter-strain variability. OA does not occur spontaneously in rabbits, but can be induced via surgical intervention (i.e., meniscectomy or anterior cruciate ligament transection [ACLT]), mechanical manipulation (i.e., impact or immobilization), or chemical application (i.e., IL-1β, collagenase, etc.). The majority of rabbit OA studies employ the ACLT model as it offers several advantages. ACLT-modified rabbits very quickly develop a wide variety of cartilage lesions post-surgically, which closely approximate many aspects of human OA. The histopathology of the rabbit ACLT model has been studied extensively and a standardized nomenclature and scoring scheme for evaluating and comparing alterations in joint structures, including changes in cartilage, synovium and bone, have been proposed. Further, a sizeable body of data derived from this model has already been amassed describing OA pathogenesis including imaging studies and effects of various potential pharmacological applications. [2]
References
1. Poole, R. et al. (2010) Recommendations for the use of preclinical models in the study and treatment of osteoarthritis. Osteoarthritis Cartilage 18(Suppl. 3):S10-S16.
2. Laverty, S. et al. (2010) The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage 18(Suppl. 3):S53-S65.
