Animal Model of Osteoarthritis

Osteoarthritis (OA) is the most common arthritis which leads to chronic disability. Because patients usually present at medical care at an advanced stage of disease, research on pathogenesis of OA using human subjects is difficult. Therefore, animal models of OA are used extensively in search of pathogenesis of degenerative joint disease and in search of potential disease modifying anti-OA drugs. For induction of OA, chemical and surgical methods have been employed widely due to several advantages, such as faster onset of disease and reproducible induction of arthritic change. Intra-articular injection of a chemical such as monosodium iodoacetate or collagenase can cause the degeneration of cartilage and the development of osteoarthritis by inhibition of the activity of glyceraldehyde-3phosphate dehydrogenase in chondrocytes or by induction of synovial inflammation and degeneration of supporting structure and resultant instability, respectively. Surgical induction involves destabilizing the knee joint by transection of the cranial cruciate ligament, collateral ligaments, or meniscotibial ligament with or without removing all or part of the meniscus. Surgical models are used not only in small animals but also in larger animals such as rabbits, sheep and dogs. Additionally, genetically modified mouse models offer opportunities to look into a specific role of a molecule or signaling pathway in the joint degradation. On the other hand, whether these models, chemically or surgically induced, or genetically modified, properly represent human OA is a critical question. Except for a limited number of cases, most human OA develops insidiously over decades without significant antecedent knee injury. In this sense, spontaneous model which develops in mice and guinea pigs might more closely resemble human OA. In this review, widely used animal models of OA are presented, focusing on the methods of its induction, their use for determining the pathophysiology of OA, and advantages and limitations of its use.