Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced experimental osteoarthritis in rats: relevance to human disease
Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced experimental osteoarthritis in rats: relevance to human disease
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DOI：
10.1016/j.joca.2007.03.014
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发表时间：
2007-10-01
影响因子：
7
通讯作者：
Head, R. D.
中科院分区：
文献类型：
--
作者：
Barve, R. A.;Minnerly, J. C.;Head, R. D.
目的：对大鼠碘乙酸钠（MIA）诱导的骨关节炎（OA）模型进行表征，并确定该模型对人类疾病的可移植性。这是通过途径、网络和系统水平比较动物和人类疾病软骨产生的转录谱来完成的。方法：每个膝关节单次注射200 μ g MIA，持续2或4周，诱导大鼠股胫关节骨关节炎表型。组织学证实了大鼠关节病变的形成。使用安捷伦大鼠全基因组微阵列测量基因表达变化。从人类膝盖上采集软骨，使用安捷伦人体阵列测量基因表达变化。结果：1443个寡核苷酸在MIA模型中差异表达，其中约三分之二表达上调。相比之下，在人类疾病组织中差异表达的2130个寡核苷酸中，大约三分之二下调。这种戏剧性的差异在每个比较阶段都可以观察到。大鼠与人在同一方向上调节的基因总重叠量小于4%。基质降解和炎症基因在MIA中的差异调节程度远高于人类疾病组织。结论：本研究通过多层次分析表明，大鼠MIA和人CA源性软骨之间的转录相似性很小。由于潜在治疗剂的疾病调节活动通常不能从动物模型转化为人类疾病，因此本研究和类似研究可能为理解这种差异提供基础。(C) 2007国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: The objective of this study was to characterize the rat monosodium iodoacetate (MIA)-induced model for ostecarthritis (OA) and determine the translatability of this model to human disease. This was accomplished through pathway, network and system level comparisons of transcriptional profiles generated from animal and human disease cartilage.Methods: An OA phenotype was induced in rat femorotibial joints following a single injection of 200 mu g MIA per knee joint for a period of 2 or 4 weeks. Lesion formation in the rat joints was confirmed by histology. Gene expression changes were measured using the Agilent rat whole genome microarrays. Cartilage was harvested from human knees and gene expression changes were measured using the Agilent human arrays.Results: One thousand nine hundred and forty-three oligos were differentially expressed in the MIA model, of these, approximately two-thirds were up-regulated. In contrast, of the 2130 differentially expressed oligos in human disease tissue, approximately two-thirds were down-regulated. This dramatic difference was observed throughout each level of the comparison. The total overlap of genes modulated in the same direction between rat and human was less than 4%. Matrix degradation and inflammatory genes were differentially regulated to a much greater extent in MIA than human disease tissue.Conclusion: This study demonstrated, through multiple levels of analysis, that little transcriptional similarity exists between rat MIA and human CA derived cartilage. As disease modulatory activities for potential therapeutic agents often do not translate from animal models to human disease, this and like studies may provide a basis for understanding the discrepancies. (C) 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.