Comparative analysis of gene, expression profiles in intact and damaged regions of human osteoarthritic cartilage
Comparative analysis of gene, expression profiles in intact and damaged regions of human osteoarthritic cartilage
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DOI：
10.1002/art.21638
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发表时间：
2006-03-01
影响因子：
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通讯作者：
Nakajima, T
中科院分区：
文献类型：
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作者：
Sato, T;Konomi, K;Nakajima, T
Objective.分析膝骨关节炎（OA）患者同一膝关节软骨完整区和受损区软骨细胞基因表达谱的差异。我们比较了从膝关节OA患者中获得的完整和受损软骨区域（根据Mankin量表分类）的信使RNA表达谱。五对OA软骨的完整和受损区域进行了评估，通过寡核苷酸阵列分析，使用双体外转录扩增技术。通过实时定量聚合酶链反应（PCR）扩增证实了微阵列数据，并与先前发表的数据进行了比较。约1，500个转录本，相当于表达转录本的8%，在软骨组织对之间显示出大于或等于2倍的表达差异。大约10%的这些转录本（n = 151）通常在5例患者样本中表达。因此，选择了114个基因（35个基因以完整>受损表达; 79个基因以完整<受损表达）。与伤口愈合过程相关的一些基因的表达，包括细胞增殖和间质胶原合成，在受损区域比在完整区域更高，与抑制基质降解的基因的发现相似。实时定量PCR数据与先前报道的数据的比较支持我们的微阵列数据的有效性。OA软骨的完整和受损区域之间的差异在5名患者中表现出相似的模式，表明存在导致软骨破坏的共同机制。阐明这一机制对于开发有效的OA治疗方法非常重要。
Objective. To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.Methods. We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real-time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data.Results. About 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed greater than or equal to 2-fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n = 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound-healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real-time quantitative PCR data with the previously reported data support the validity of our microarray data.Conclusion. Differences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA.