Xu Wei, Liang Chao-Ge, Li Yi-Fan, Ji Yun-Han, Qiu Wen-Jun, Tang Xian-Zhong
Department of Orthopedic Surgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200336, P.R. China.
Int J Clin Exp Pathol. 2015 Mar 1;8(3):2737-45. eCollection 2015.
We aimed to investigate the role of Notch1/Hes signaling pathway in the pathogenesis of abnormal ossification of hip ligament in patients with ankylosing spondylitis (AS). 22 AS patients scheduled for artificial hip arthroplasty were randomly chosen as AS group. As controls, we used 4 patients diagnosed with transcervical fracture who underwent hip replacement surgery. Notch1 and Hes mRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR). Immunohistochemistry (IHC) was used to detect Notch1 and Hes protein expression. Correlation analyses of Notch-l and Hes with AS-related clinical factors were conducted with spearman's correlation analysis and partial correlation analysis. RFQ-PCR results showed significant differences in Notch1 and Hes mRNA expressions between AS group and the control group (all P<0.05). IHC analysis further indicated positive nuclear signals of Notch1 and Hes protein, indicating functional activation of the Notch1 and Hes pathways. Semi-quantitative IHC showed a higher Notch1 and Hes expression levels in AS group compared to the control group (all P<0.05). Correlation analysis suggested that Hes protein expression was positively associated with the clinical course of the disease in AS patients. In conclusion, Notch1 and Hes overexpression was clearly detected in hip joint ligaments of AS patients, Hes protein expression was associated with the clinical course of AS. Taken together, we suggest that signaling pathways mediated by Notch1-Hes may contribute to ligament ossification of hip joints in AS patients.
我们旨在研究Notch1/Hes信号通路在强直性脊柱炎(AS)患者髋关节韧带异常骨化发病机制中的作用。随机选取22例行人工髋关节置换术的AS患者作为AS组。作为对照,我们选取了4例诊断为经颈型骨折并接受髋关节置换手术的患者。采用实时荧光定量聚合酶链反应(RFQ-PCR)检测Notch1和Hes mRNA表达。采用免疫组织化学(IHC)检测Notch1和Hes蛋白表达。采用Spearman相关分析和偏相关分析对Notch1和Hes与AS相关临床因素进行相关性分析。RFQ-PCR结果显示,AS组与对照组Notch1和Hes mRNA表达存在显著差异(均P<0.05)。IHC分析进一步显示Notch1和Hes蛋白的核阳性信号,表明Notch1和Hes信号通路功能激活。半定量IHC显示,AS组Notch1和Hes表达水平高于对照组(均P<0.05)。相关性分析表明,AS患者中Hes蛋白表达与疾病临床病程呈正相关。总之,在AS患者髋关节韧带中明显检测到Notch1和Hes过表达,Hes蛋白表达与AS临床病程相关。综上所述,我们认为Notch1-Hes介导的信号通路可能促成AS患者髋关节韧带骨化。