Validity evaluation of a rat model of monoiodoacetate-induced osteoarthritis with clinically effective drugs

BACKGROUND: Knee osteoarthritis (KOA) is the most common type of joint disease in elderly people and is characterized by pain and dysfunction. Although the monoiodoacetate (MIA)-induced model is widely used as a rodent KOA model, it is important to acknowledge the inherent limitations of this model, as the MIA model develops complex pathological phases on a daily basis. An accurate understanding of this model and the selection of an appropriate time point according to the target for drug candidates can lead to the development of clinically effective drugs. METHODS: Changes in the pathological state of the MIA model were assessed via histopathological evaluation. Clodronate, a bisphosphonate, and diclofenac, a nonsteroidal anti-inflammatory drug (NSAID), were selected as models of clinically effective drugs due to their different mechanisms of action. The analgesic effects of both drugs on the MIA model were evaluated. The long-term effect of clodronate on subchondral bone osteoclasts was also evaluated. RESULTS: Histopathological evaluation revealed that MIA-induced symptomatic behavior occurred in the early and late phases and was accompanied by synovial inflammation and osteoclast-related joint degeneration, respectively. Although clodronate inhibited symptomatic behavior and prevented cartilage degeneration from the early to late phases, diclofenac inhibited symptomatic behavior only in the early phase. Clodronate acted locally and inhibited the activation of subchondral osteoclasts. CONCLUSIONS: Pathological changes, such as synovial changes in the early phase and knee joint degeneration in the late phase, in the MIA model are similar to those in human KOA. Our results indicate that the early phase in the MIA model is appropriate for evaluating the effects of anti-inflammatory agents such as NSAIDs and corticosteroids. The late phase in the MIA model is appropriate for evaluating the effects of drugs that act on cartilage and subchondral bone.