ANIMAL-MODELS USED TO EVALUATE ANTI-OSTEO ARTHRITIS DRUGS

Naturally occuring osteoarthritis occurs in a variety of animal specie s including mice, guinea pigs, dogs and cynomolgus macaques and some o f these animals have been used to evaluate the ability of anti-osteoar thritis drugs to reduce synovial inflammation and preserve cartilage i ntegrity. However, the genetically determined animal models of osteoar thritis require the establishement of colonies which may take several years to develop and may be influenced by the strain of animal used an d ill-defined environmental factors; On the other hand, the injection of irritants or enzymes into joints, or destabilization by surgical me ans, can rapidly and reproducibly lead to joint arthropathy and has th erefore been more widely used. Although small animals, particularly ra ts and rabbits, have been the favoured target species, large animals s uch as dogs and sheep offer many advantages including the opportunity to undertake topographical analysis of joint cartilage and serial aspi ration of synovial fluid. Meniscectomy is a common orthopaedic procedu re which, in man and animals, is known to lead to osteoarthritis. In t he past we have used this technique to induce osteoarthritis in pure b red dogs but more recently we have employed pure bred Merino sheep, wh ich were matched for age, sex and weight. Using this ovine model we ha ve been able to monitor the early and intermediate stages of cartilage metabolism, as well as identify key proteinases responsible for the l oss 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 oste oarthritis.