Rodent Model Of Osteoarthritis Research Articles

Evaluation of disease progression during nonsteroidal antiinflammatory drug treatment: experimental models

OSTEOARTHRITIS (OA) is a disorder of multifactorial etiology which can take several decades to progress in man. The early phases, which are normally asymptomatic, are characterized by focal cartilage lesions accompanied by cartilage and bone hypertrophy. With progression, cartilage becomes extensively eroded, exposing bone. The bone shows areas of necrosis and active remodeling. A synovitis may become established leading to leukocyte infiltration, capsular thickening and altered synovial cell metabolism. The altered synovial cell metabolism is reflected in reduced synthesis of hyaluronan, the visco-elastic component of synovial fluid. These multiple time-dependent events are di$cult to reproduce collectively in animal models and impossible to simulate in vitro. For these reasons the evaluation of the e#ects of nonsteroidal antiinflammatory drugs (NSAIDs) on the progression of OA in models has, for the most part, focused on specific joint tissues, particularly cartilage and bone. Rodent models of OA have generated conflicting results on the e#ects of NSAIDs on cartilage metabolism. The models have included (1) OA induced by surgical destabilization of joints; (2) OA induced by injection of enzymes or chemicals into joints; (3) OA induced by selective breeding to intensify a genetic defect. The di#erent etiologies, variable rates of progression and doses/routes of drugs administered could account for these discrepancies. Large animal models of traumatic OA o#er many advantages over rodent models. If pure bred animals of similar sex and weight are used, the induced lesions are reproducible, are slower to progress and correspond more faithfully to the pathological changes which occur in human OA joints. Moreover, since the joints are larger, topographical sampling of cartilage and subchondral bone can be undertaken and synovial