Sodium Iodoacetate-Induced Experimental Osteoarthritis and Associated Pain Model in Rats

Abstract

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...

A Novel Rat Model of Ankle Osteoarthritis Induced by the Application of Monoiodoacetate

“…These results are similar to those of the previous study about the rat model of knee OA. MIA has been shown to inhibit chondrocyte metabolism and promote apoptosis [15], and its injection was found to induce various histological changes similar to those in human OA [15,16]. Kobayashi et al [16] reported that an intra-articular injection of MIA induced OA-like histopathologic changes and a loss of proteoglycan from cartilage tissue in the knee joint in a dose-dependent manner.…”

“…MIA has been shown to inhibit chondrocyte metabolism and promote apoptosis [15], and its injection was found to induce various histological changes similar to those in human OA [15,16]. Kobayashi et al [16] reported that an intra-articular injection of MIA induced OA-like histopathologic changes and a loss of proteoglycan from cartilage tissue in the knee joint in a dose-dependent manner. A MIAinduced model of knee OA was established and has been used in some studies [7][8][9][10]15,16].…”

“…Kobayashi et al [16] reported that an intra-articular injection of MIA induced OA-like histopathologic changes and a loss of proteoglycan from cartilage tissue in the knee joint in a dose-dependent manner. A MIAinduced model of knee OA was established and has been used in some studies [7][8][9][10]15,16]. We investigated the relationship between pain related behaviors and structural pathology of the ankle joint following MIA injection on single day or 2 consecutive days.…”

Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity

“…The injection of MIA in the knee joint induces necrosis of chondrocytes with decrease of cartilage thickness and osteolysis [19]. Kobayashi et al showed that MIA is able to disorganize chondrocytes and to promote cartilage erosion [20]. These alterations are comparable with joint damages typical of humans affected by osteoarthritis [21e23].…”

Protective Effects of Human Placenta Extract on Cartilage Degradation in Experimental Osteoarthritis

“…Histopathological changes in each animal were quantitatively expressed by three grades for each finding. 14) Grading was done under the authority of Medplan Pathology Laboratories, Seoul, Korea.…”