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

IF 2.2 3区 医学 Q2 ORTHOPEDICS
Yamato Sasaki, Kei Kijima, Keiji Yoshioka
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引用次数: 0

Abstract

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.

临床有效药物对单碘乙酸盐致骨关节炎大鼠模型的有效性评价。
背景:膝关节骨性关节炎(KOA)是老年人最常见的关节疾病,以疼痛和功能障碍为特征。虽然单碘乙酸酯(MIA)诱导的模型被广泛用于啮齿动物KOA模型,但重要的是要认识到该模型的固有局限性,因为MIA模型每天都会发展出复杂的病理阶段。准确理解这一模型,根据候选药物的靶点选择合适的时间点,可以开发出临床有效的药物。方法:通过组织病理学评价MIA模型病理状态的变化。由于双膦酸盐氯膦酸钠和非甾体抗炎药双氯芬酸的作用机制不同,我们选择它们作为临床有效药物的模型。评价两种药物对MIA模型的镇痛作用。对氯膦酸钠对软骨下破骨细胞的长期影响也进行了评价。结果:组织病理学评估显示,mia诱导的症状性行为发生在早期和晚期,分别伴有滑膜炎症和破骨细胞相关关节变性。虽然氯膦酸钠能抑制症状行为并从早期到晚期阻止软骨退变,但双氯芬酸仅在早期抑制症状行为。氯膦酸钠局部起作用,抑制软骨下破骨细胞的活化。结论:MIA模型早期滑膜改变、晚期膝关节退行性变等病理变化与人类KOA相似。我们的研究结果表明,MIA模型的早期阶段适合评估抗炎药(如非甾体抗炎药和皮质类固醇)的作用。MIA模型的后期适合于评估作用于软骨和软骨下骨的药物的作用。
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来源期刊
BMC Musculoskeletal Disorders
BMC Musculoskeletal Disorders 医学-风湿病学
CiteScore
3.80
自引率
8.70%
发文量
1017
审稿时长
3-6 weeks
期刊介绍: BMC Musculoskeletal Disorders is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of musculoskeletal disorders, as well as related molecular genetics, pathophysiology, and epidemiology. The scope of the Journal covers research into rheumatic diseases where the primary focus relates specifically to a component(s) of the musculoskeletal system.
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