Animal models of osteoarthritis: lessons learned while seeking the 'Holy Grail'

Purpose of review Difficulties in studying osteoarthritis in humans that stem from both the low sensitivity of diagnostic tools and the low availability of diseased tissues explain why research on animal models remains highly dynamic. This review will summarize the recent advances in this field. Recent findings With regard to the etiology of osteoarthritis, synovial macrophages mediate osteophyte formation, whereas increased ligament laxity could be responsible for spontaneous osteoarthritis in guinea pigs. The concomitant changes in subchondral bone and cartilage reported in several models, and the structure-modifying effects of some bone inhibitors have confirmed the importance of bone in osteoarthritis. With regard to cartilage pathobiology, ADAMTS-5 is the major aggrecanase responsible for cartilage destruction, whereas inadequate control of oxidative stress and decreased expression of transforming growth factor-beta receptors could predispose to osteoarthritis. New models include a postmenopausal rat model, the groove model and a joint-specific bone morphogenetic receptor-deficient mouse. The iodoacetate model was also validated as the first pain model of osteoarthritis. Summary In view of the multiple animal models available, there is a need to reach a consensus on one or several gold standard animal model(s). New studies indicate that important differences in therapeutic response exist between young and old animals, and between spontaneous and surgical models, suggesting that not all models are adequate models of osteoarthritis.