Wu Shi-xun, Guo Xiong, Liu Jiang-tao, Zhang Zeng-tie, Dennis Bannel S, Zhang Yin-gang
Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, First Affiliated Hospital, Xi an Jiaotong University College of Medicine, Xi an 710061, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2011 Nov;31(11):1851-4.
To investigate the changes in the expressions of Fas-associated death domain protein (FADD) and cellular-FLICE inhibitory protein (c-FLIP) in the articular cartilage of patients with Kashin-Beck disease (KBD) and the role of these proteins in the pathogenesis of KBD.
The cartilage samples were collected from patients with established diagnosis of KBD and osteoarthritis and from healthy control subjects undergoing amputation due to traffic accidents. The expressions of Fas-associated death domain protein (FADD) and cellular-FLICE inhibitory protein (c-FLIP) in the cartilage were detected by immunohistochemistry, and the positive chondrocytes were counted in different layers of the articular cartilage under microscope.
The positivity rates of FADD in the middle layer of articular cartilage from patients with KBD [(28.68∓2.19)%] and osteoarthritis [(35.40∓2.34)%] were significantly higher than that in normal cartilage [(10.51∓5.02)%, F=16.245, P=0.000], but the rates in the upper and deeper layers were comparable among the 3 groups (P=0.206-0.761). In KBD cartilage, FADD expression was the highest in the middle layer [(28.68∓5.38)%] followed by the deeper layer [(17.94∓8.38)%]. Compared with the healthy controls, KBD and osteoarthritis patients showed significantly higher FLIP expression in the upper layer of the cartilage (F=5.929, P=0.018) but similar expressions in middle and deeper layers.
KBD patients have significant increased FADD expression in the middle layer but decreased FLIP expression in the upper layer of the cartilage, suggesting that the death receptor pathway and its regulators play important roles in the pathogenesis of KBD.
探讨大骨节病(KBD)患者关节软骨中Fas相关死亡结构域蛋白(FADD)和细胞型FLICE抑制蛋白(c-FLIP)表达的变化及其在KBD发病机制中的作用。
收集确诊为KBD和骨关节炎患者以及因交通事故截肢的健康对照者的软骨样本。采用免疫组织化学法检测软骨中Fas相关死亡结构域蛋白(FADD)和细胞型FLICE抑制蛋白(c-FLIP)的表达,并在显微镜下对关节软骨不同层次的阳性软骨细胞进行计数。
KBD患者[(28.68±2.19)%]和骨关节炎患者[(35.40±2.34)%]关节软骨中层FADD阳性率显著高于正常软骨[(10.51±5.02)%,F=16.245,P=0.000],但3组上层和深层的阳性率差异无统计学意义(P=0.206~0.761)。KBD软骨中,中层FADD表达最高[(28.68±5.38)%],其次为深层[(17.94±8.38)%]。与健康对照组相比,KBD和骨关节炎患者软骨上层FLIP表达显著升高(F=5.929,P=0.018),但中层和深层表达相似。
KBD患者软骨中层FADD表达显著增加,而上层FLIP表达降低,提示死亡受体途径及其调节因子在KBD发病机制中起重要作用。