Chou C-H, Lee M T M, Song I-W, Lu L-S, Shen H-C, Lee C-H, Wu J-Y, Chen Y-T, Kraus V B, Wu C-C
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; National Center for Genome Medicine, Academia Sinica, Taipei, Taiwan; Department of Pathology, Duke University School of Medicine, Durham, NC, USA.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; National Center for Genome Medicine, Academia Sinica, Taipei, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Yokohama, Japan.
Osteoarthritis Cartilage. 2015 Apr;23(4):571-80. doi: 10.1016/j.joca.2014.12.020. Epub 2015 Jan 7.
To identify disease relevant genes and pathways associated with knee Osteoarthritis (OA) progression in human subjects using medial and lateral compartment dominant OA knee tissue.
Gene expression of knee cartilage was comprehensively assessed for three regions of interest from human medial dominant OA (n = 10) and non-OA (n = 6) specimens. Histology and gene expression were compared for the regions with minimal degeneration, moderate degeneration and significant degeneration. Agilent whole-genome microarray was performed and data were analyzed using Agilent GeneSpring GX11.5. Significant differentially regulated genes were further investigated by Ingenuity Pathway Analysis (IPA) to identify functional categories. To confirm their association with disease severity as opposed to site within the knee, 30 differentially expressed genes, identified by microarray, were analyzed by quantitative reverse-transcription polymerase chain reaction on additional medial (n = 16) and lateral (n = 10) compartment dominant knee OA samples.
A total of 767 genes were differentially expressed ≥ two-fold (P ≤ 0.05) in lesion compared to relatively intact regions. Analysis of these data by IPA predicted biological functions related to an imbalance of anabolism and catabolism of cartilage matrix components. Up-regulated expression of IL11, POSTN, TNFAIP6, and down-regulated expression of CHRDL2, MATN4, SPOCK3, VIT, PDE3B were significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples.
Our study provides a strategy for identifying targets whose modification may have the potential to ameliorate pathological alternations and progression of disease in cartilage and to serve as biomarkers for identifying individuals susceptible to progression.
利用内侧和外侧间室为主的膝骨关节炎（OA）膝关节组织，鉴定与人类受试者膝骨关节炎进展相关的疾病相关基因和通路。
对来自人类内侧为主的OA（n = 10）和非OA（n = 6）标本的三个感兴趣区域的膝关节软骨基因表达进行综合评估。比较了轻度退变、中度退变和重度退变区域的组织学和基因表达。进行了安捷伦全基因组微阵列检测，并使用安捷伦GeneSpring GX11.5分析数据。通过 Ingenuity 通路分析（IPA）进一步研究显著差异调节的基因，以确定功能类别。为了确认它们与疾病严重程度而非膝关节内部位的关联，通过定量逆转录聚合酶链反应对另外16例内侧和10例外侧间室为主的膝OA样本分析了微阵列鉴定出的30个差异表达基因。
与相对完整区域相比，病变中共有767个基因差异表达≥两倍（P≤0.05）。通过IPA对这些数据的分析预测了与软骨基质成分合成代谢和分解代谢失衡相关的生物学功能。IL11、POSTN、TNFAIP6的上调表达以及CHRDL2、MATN4、SPOCK3、VIT、PDE3B的下调表达与OA进展显著相关，并在内侧和外侧间室为主的OA样本中得到验证。
我们的研究提供了一种策略，用于鉴定其修饰可能有潜力改善软骨中疾病的病理改变和进展并作为识别易进展个体的生物标志物的靶点。
