Duan Chen, Guo Xiong, Zhang Xiao-Dong, Yu Han-Jie, Yan Hua, Gao Ying, Ma Wei-Juan, Gao Zong-Qiang, Xu Peng, Lammi Mikko
Medical College of Xi'an Jiaotong University, Number 76 Yan Ta, West Road, Xi'an, Shaanxi 710061, China.
Arthritis Rheum. 2010 Mar;62(3):771-80. doi: 10.1002/art.27282.
To investigate the differences in gene expression profiles of adult articular cartilage from patients with Kashin-Beck disease (KBD) versus those with primary knee osteoarthritis (OA).
The messenger RNA expression profiles of articular cartilage from patients with KBD, diagnosed according to the clinical criteria for KBD in China, were compared with those of cartilage from patients with OA, diagnosed according to the Western Ontario and McMaster Universities OA Index. Total RNA was isolated separately from 4 pairs of the KBD and OA cartilage samples, and the expression profiles were evaluated by Agilent 4x44k Whole Human Genome density oligonucleotide microarray analysis. The microarray data for selected transcripts were confirmed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) amplification.
For 1.2 x 10(4) transcripts, corresponding to 58.4% of the expressed transcripts, 2-fold changes in differential expression were revealed. Expression levels higher in KBD than in OA samples were observed in a mean + or - SD 6,439 + or - 1,041 (14.6 + or - 2.4%) of the transcripts, and expression levels were lower in KBD than in OA samples in 6,147 + or - 1,222 (14.2 + or - 2.8%) of the transcripts. After application of the selection criteria, 1.85% of the differentially expressed genes (P < 0.001 between groups) were detected. These included 233 genes, of which 195 (0.4%) were expressed at higher levels and 38 (0.08%) were expressed at lower levels in KBD than in OA cartilage. Comparisons of the quantitative RT-PCR data supported the validity of our microarray data.
Differences between KBD and OA cartilage exhibited a similar pattern among all 4 of the pairs examined, indicating the presence of disease mechanisms, mainly chondrocyte matrix metabolism, cartilage degeneration, and apoptosis induction pathways, which contribute to cartilage destruction in KBD.
研究大骨节病（KBD）患者与原发性膝关节骨关节炎（OA）患者成人关节软骨基因表达谱的差异。
将按照中国大骨节病临床诊断标准确诊的KBD患者关节软骨的信使核糖核酸（mRNA）表达谱，与按照西安大略和麦克马斯特大学骨关节炎指数确诊的OA患者软骨的表达谱进行比较。分别从4对KBD和OA软骨样本中分离总RNA，采用安捷伦4x44k全人类基因组密度寡核苷酸微阵列分析评估表达谱。通过定量实时逆转录-聚合酶链反应（RT-PCR）扩增确认所选转录本的微阵列数据。
对于1.2×10⁴个转录本（占表达转录本的58.4%），发现差异表达有2倍变化。在平均±标准差为6439±1041（14.6±2.4%）的转录本中，观察到KBD样本中的表达水平高于OA样本；在6147±1222（14.2±2.8%）的转录本中，KBD样本中的表达水平低于OA样本。应用选择标准后，检测到1.85%的差异表达基因（组间P<0.001）。其中包括233个基因，与OA软骨相比，KBD中195个（0.4%）基因表达水平较高，38个（0.08%）基因表达水平较低。定量RT-PCR数据的比较支持了我们微阵列数据的有效性。
在所检测的全部4对样本中，KBD和OA软骨之间的差异呈现相似模式，表明存在主要导致软骨破坏的疾病机制，主要是软骨细胞基质代谢、软骨退变和凋亡诱导途径。
