ABSTRACT. Degenerative lesions were induced in the knee joint of Wistar rats by intraarticular injection of chondrocyte metabolism inhibitor mono-iodoacetate (MIA) at doses of 0, 0.3 or 3 mg/joint. Histopathological examination and the measurement of hind paw weight ratio as an index of joint pain by incapacitance tester were performed. Histological findings that are similar to those observe d in human osteoarthritis (OA), such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bon e exposure etc., were observed in a MIA-dose-dependent manner. Saflanin-O fast green staining revealed that marked diffuse reduction of proteoglycan in cartilage tissue of rats treated with MIA. The clinical scores of the joint pain were closely correlated to the grade of histological findings. We conclude that the present experimental model in combination with a novel dual channel weight averager would be very useful for the study of human OA, and could be applied for estimation of therapeutic effect of new anti-OA drugs. KEY WORDS: mono-iodoacetate, osteoarthritis, pain assessment, rat.J. Vet. Med. Sci. 65(11): 1195-1199, 2003 Osteoarthritis (OA) is a degenerative joint disease characterized by fibrillation and erosion in cartilage tissue, chondrocyte proliferation and osteophyte formation at the joint margins, and sclerosis of subchondral bone [13]. Reportedly, imbalance occurs between synthetic and degenerative process within chondrocytes that leads to the net loss of cartilage tissue and subsequent pathologic condition [2]. At late stage of human OA, articular damages eventually lead to clinical findings such as joint impairment and pain.Although human OA-like lesions may occur spontaneously in dogs and mice, they are not appropriate for the evaluation of new anti-OA therapeutic agents because of low incidence and variable onset [5,16]. There are number of animal OA models that has variety of etiologies such as surgical induction [11, 12, 15], collagenase-induced [9], extracellular matrix loss [18,19], or impact-induced trauma [10]. However, studies on a new therapeutic drug for human OA and associated pain have been hampered because of the lack of useful animal model that closely mimic the human OA. Some study groups have previously reported that chondrocyte metabolism inhibitor mono-iodoacetate (MIA) have been reported to induce the disruption of glycolysis and subsequent cell death, and the loss of chondrocytes results in histologic changes in the knee joint resembling to human OA [6,17]. The objective of the present study is to clarify the histopathologic changes in MIA-induced knee joint lesion in the rats and its correlation to the dose of MIA and clinical pain evaluated by dual channel weight averager, with a development trial of non-invasive rat OA model for new drug development.
MATERIALS AND METHODS
Animals:Seven weeks old female Wistar rats were purchased from Charles River Japan Inc. (Yokohama, Kanagawa) and kept in air-conditioned animal room at 22°C and given tap water...
