Menisectomized miniature Vietnamese pigs develop articular cartilage pathology resembling osteoarthritis

Menisectomized miniature Vietnamese pigs develop articular cartilage pathology resembling osteoarthritis
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DOI:
10.1016/j.prp.2015.07.012
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发表时间:
2015-01-01
影响因子:
2.8
通讯作者:
Vega-Lopez, Marco A.
Vega-Lopez, Marco A.
中科院分区:
医学4区
文献类型:
--
作者:
Cruz, Raymundo;Ramirez, Carmen;Vega-Lopez, Marco A.

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动物模型已被用于了解骨关节炎(OA)的基本生物学,并有助于确定新的候选生物标志物,用于这种疾病的早期诊断和治疗。小动物不能充分模拟人类疾病;因此,需要大型动物模型。猪被用作人类疾病的模型,因为它们在解剖学,生理学和基因组方面与人类相似。因此,我们分析了越南小型猪单侧部分骨关节切除术和20天运动方案后的关节软骨和滑膜病理学,以确定猪是否发展出与人类OA相似的病理学特征。对切除关节的猪的关节软骨的组织学和蛋白表达分析揭示了以下类似于OA的病理变化:纤维化、裂隙、软骨细胞簇形成、蛋白多糖含量减少以及OA相关蛋白MMP-3、MMP-T13、半胱氨酸天冬氨酸蛋白酶原-3和IL-13的上调。此外,滑膜的组织学分析显示轻度滑膜炎,其特征在于增生、细胞浸润和新血管生成。在对侧关节和假手术猪的关节中未观察到病理变化。需要进一步的研究来验证这种OA模型,然而,我们的研究结果可以鼓励使用猪来研究OA的早期病理生理学。基于它们与人类的相似性,猪可能有助于临床前研究,以确定新的候选生物标志物和新的OA治疗方法。(C)2015 Elsevier GmbH. All rights reserved.
Animal models have been used to understand the basic biology of osteoarthritis (OA) and have helped to identify new candidate biomarkers for the early diagnosis and treatment of this condition. Small animals cannot sufficiently mimic human diseases; therefore, large animal models are needed. Pigs have been used as models for human diseases because they are similar to humans in terms of their anatomy, physiology and genome. Hence, we analyzed articular cartilage and synovial membrane pathology in miniature Vietnamese pigs after a unilateral partial menisectomy and 20-day exercise regimen to determine if the pigs developed pathological characteristics similar to human OA. Histological and protein expression analysis of articular cartilage from menisectomized pigs revealed the following pathologic changes resembling OA: fibrillation, fissures, chondrocyte cluster formation, decrease in proteoglycan content and upregulation of the OA-associated proteins MMP-3, MMP-T13, procaspase-3 and IL-I 3. Moreover, histological analysis of synovial membrane revealed mild synovitis, characterized by hyperplasia, cell infiltration and neoangiogenesis. Pathological changes were not observed in the contralateral joints or the joints of sham-operated pigs. Further studies are required to validate such an OA model; however, our results can encourage the use of pigs to study early stages of OA physiopathology. Based on their similarities to humans, pigs may be useful for preclinical studies to identify new candidate biomarkers and novel treatments for OA. (C) 2015 Elsevier GmbH. All rights reserved.