Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, 168 Changhai Road, Shanghai 200433, People's Republic of China.
Clin Rheumatol. 2012 Oct;31(10):1479-91. doi: 10.1007/s10067-012-2038-9. Epub 2012 Aug 18.
To investigate the pathogenesis of abnormal ossification of the hip ligament in patients with ankylosing spondylitis (AS) by comparing gene expression profiles of the hip ligament in patients with AS to those in normal persons using DNA microarray technology, we studied 18 patients with AS (case group) who underwent total hip arthroplasty in our department from March 1, 2009 to January 31, 2010 and compared them with 6 patients with femoral neck fracture (control group) who underwent total hip replacement. We screened the first five patients in each group with the HumanWG-6 v3.0 Expression BeadChip. Compared to the control group, 519 genes in the case group showed statistically significant differences. Among these, there were 238 upregulated genes and 196 downregulated genes. Gene Ontology (GO) classification showed that differential genes in the hip joint ligaments of patients with AS were involved in immunity, cell adhesion, membrane transport, sugar metabolism, polysaccharide synthesis and metabolism, and cell motility. The Kyoto Encyclopedia of Genes and Genomes classification showed that these differential genes were involved in B cell receptor signaling pathways, adherens junction, protein export, fructose and mannose metabolism, T cell receptor signaling pathways, keratin sulfate biosynthesis, N-glycan biosynthesis, and regulation of the actin cytoskeleton. We tested 2 genes from the screened differential genes in 18 case patients and 6 control cases using real-time polymerase chain reaction. The results demonstrated that the expression of the B4GALT3 gene in the case group was 15.32 times higher than that in the control group (P < 0.01), and the expression of the RBP5 gene in the case group was 4.09 times higher than that in the control group (P < 0.01). This conformed to the microarray analysis. Our preliminary data suggest that differential gene expression in patients with AS includes the immune system, intracellular or extracellular signaling pathway, and bone matrix biosynthesis pathway, which might play important roles in hip joint ligament ossification.
为了通过 DNA 微阵列技术比较强直性脊柱炎（AS）患者髋关节韧带的基因表达谱，研究髋关节韧带异常骨化的发病机制，我们研究了 2009 年 3 月 1 日至 2010 年 1 月 31 日在我科接受全髋关节置换术的 18 例 AS 患者（病例组），并与 6 例股骨颈骨折（对照组）患者进行了比较。我们使用 HumanWG-6 v3.0 Expression BeadChip 对每组前 5 例患者进行了筛查。与对照组相比，病例组有 519 个基因差异表达，其中 238 个上调基因和 196 个下调基因。GO 分类显示，AS 患者髋关节韧带差异基因参与免疫、细胞黏附、膜转运、糖代谢、多糖合成和代谢以及细胞运动。京都基因与基因组百科全书分类显示，这些差异基因参与 B 细胞受体信号通路、黏着连接、蛋白输出、果糖和甘露糖代谢、T 细胞受体信号通路、角蛋白硫酸盐生物合成、N-糖基生物合成和肌动蛋白细胞骨架调节。我们使用实时聚合酶链反应对从筛选出的差异基因中检测了 18 例病例患者和 6 例对照患者中的 2 个基因。结果表明，病例组的 B4GALT3 基因表达是对照组的 15.32 倍（P<0.01），病例组的 RBP5 基因表达是对照组的 4.09 倍（P<0.01）。这与微阵列分析结果一致。我们的初步数据表明，AS 患者的差异基因表达包括免疫系统、细胞内或细胞外信号通路和骨基质生物合成途径，这些途径可能在髋关节韧带骨化中发挥重要作用。
