[Animal models used for the evaluation of anti-osteoarthritis drugs]

Naturally occurring osteoarthritis occurs in a variety of animal species including mice, guinea pigs, dogs and cynomolgus macaques and some of these animals have been used to evaluate the ability of anti-osteoarthritis drugs to reduce synovial inflammation and preserve cartilage integrity. However, the genetically determined animal models of osteoarthritis require the establishment of colonies which may take several years to develop and may be influenced by the strain of animal used and ill-defined environmental factors. On the other hand, the injection of irritants or enzymes into joints, or destabilization by surgical means, can rapidly and reproducibly lead to joint arthropathy and has therefore been more widely used. Although small animals, particularly rats and rabbits, have been the favoured target species, large animals such as dogs and sheep offer many advantages including the opportunity to undertake topographical analysis of joint cartilage and serial aspiration of synovial fluid. Meniscectomy is a common orthopaedic procedure which, in man and animals, is known to lead to osteoarthritis. In the past we have used this technique to induce osteoarthritis in pure bred dogs but more recently we have employed pure bred Merino sheep, which were matched for age, sex and weight. Using this ovine model we have been able to monitor the early and intermediate stages of cartilage metabolism, as well as identify key proteinases responsible for the loss of proteoglycans from these tissues in osteoarthritis. The effects of anti-osteoarthritis drugs on inflammatory mediators and cartilage metabolism has been successfully studied using the ovine model of osteoarthritis.