Mono-iodoacetate-induced experimental osteoarthritis - A dose-response study of loss of mobility, morphology, and biochemistry
Mono-iodoacetate-induced experimental osteoarthritis - A dose-response study of loss of mobility, morphology, and biochemistry
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DOI：
10.1002/art.1780400917
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发表时间：
1997-09-01
影响因子：
--
通讯作者：
Gillet, P
中科院分区：
文献类型：
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作者：
Guingamp, C;GegoutPottie, P;Gillet, P
目的：研究单碘乙酸（MIA）诱导的大鼠骨关节炎（OA）中软骨形态学和生化变化与活动度的剂量反应性。通过生物遥测术评估大鼠活动性。关节病变仅通过肉眼和组织学检查表征。通过1，9-二甲基亚甲基蓝染料结合试验和髌骨软骨放射性硫酸盐掺入法评价软骨蛋白多糖代谢。大鼠膝关节注射MIA后，自发活动迅速、短暂且呈剂量依赖性降低（主要反应），此后，只有高剂量（0.3 mg和3.0 mg）在第15天导致继发性进行性长期自发活动丧失，此时软骨下骨vva暴露，这2个剂量导致第15天软骨蛋白聚糖浓度的显著变化，并且到第2天在外周髌骨中对抗骨炎的强烈抑制，与低剂量（0.01、0.03和0.1mg）的作用相比，结论。当使用足够剂量的MIA时，该模型可以容易且快速地在大鼠中再现OA样病变和功能障碍，类似于在人类疾病中观察到的。这些参数以及蛋白聚糖代谢可以作为研究软骨保护药物的指标，或者用于评估成像技术检测和评估软骨病变的能力。
Objective, To characterize the dose-responsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats,Methods. Rat mobility was assessed by biotelemetry. Articular lesions mere characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethglmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage,Results. Spontaneous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response), Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long-term loss of spontaneous mobility on day 15, when subchondral bone vvas exposed, These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg),Conclusion. When a sufficient dose of MIA is used, this model can easily and quickly reproduce OA-like lesions and functional impairment in rats, similar to that observed in human disease, These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect and evaluate chondral lesions.