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在骨关节炎生物标志物研究中使用动物模型。

Using animal models in osteoarthritis biomarker research.

作者信息

Garner Bridget C, Stoker Aaron M, Kuroki Keiichi, Evans Richard, Cook Cristi Reeves, Cook James L

机构信息

Department of Veterinary Pathology, University of Georgia, Athens, GA 30605, USA.

出版信息

J Knee Surg. 2011 Dec;24(4):251-64. doi: 10.1055/s-0031-1297361.

DOI:10.1055/s-0031-1297361
PMID:22303754
Abstract

Osteoarthritis (OA) is a disease that commonly affects human and veterinary patients. Animal models are routinely used for OA research, and the dog is a nearly ideal species for translational investigation of human OA biomarkers. The cytokine, chemokine, and matrix metalloprotease (MMP) profiles of synovial fluid, serum, and urine from dogs with surgically induced and naturally occurring OA were compared with dogs without OA using xMAP technology (Qiagen Inc., Valencia, CA). Markers that exhibited significant differences between groups were identified (monocyte chemoattractant protein 1 [MCP1], interleukin 8 [IL8], keratinocyte-derived chemoattractant [KC], and MMP2 and MMP3), and their sensitivities and specificities were calculated to determine their diagnostic usefulness in a future biomarker panel. Synovial fluid IL8 was the most sensitive, but MCP1 was also highly sensitive and specific. The alterations in KC suggested that it may differentiate between cruciate disease and other types of OA, and the MMPs were most sensitive and specific in the serum. This study provided additional insight to the participation of cytokines, chemokines, and MMPs in OA, and potential diagnostic biomarker candidates were identified. A brief literature review of other biomarker candidates previously examined using animal models is discussed.

摘要

骨关节炎(OA)是一种常见于人类和兽医患者的疾病。动物模型常用于骨关节炎研究,而狗是用于人类骨关节炎生物标志物转化研究的近乎理想的物种。使用xMAP技术(Qiagen公司,加利福尼亚州瓦伦西亚),将手术诱导和自然发生骨关节炎的狗的滑液、血清和尿液中的细胞因子、趋化因子和基质金属蛋白酶(MMP)谱与无骨关节炎的狗进行了比较。确定了在组间表现出显著差异的标志物(单核细胞趋化蛋白1 [MCP1]、白细胞介素8 [IL8]、角质形成细胞衍生趋化因子[KC]以及MMP2和MMP3)并计算了它们的敏感性和特异性,以确定它们在未来生物标志物组中的诊断效用。滑液IL8最敏感,但MCP1也具有高敏感性和特异性。KC的变化表明它可能区分十字韧带疾病和其他类型的骨关节炎,而MMP在血清中最敏感且特异。本研究为细胞因子、趋化因子和MMP在骨关节炎中的作用提供了更多见解,并确定了潜在的诊断生物标志物候选物。还讨论了先前使用动物模型研究的其他生物标志物候选物的简要文献综述。

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