Dai XiaoXia, Song RuiXia, Xiong YongMin
Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the people's Rupublic of China, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, China.
Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission of the people's Rupublic of China, Xi'an Jiaotong University Health Science Center, No. 76 Yanta West Road, Xi'an, Shaanxi 710061, China.
Exp Cell Res. 2017 Oct 15;359(2):337-341. doi: 10.1016/j.yexcr.2017.08.015. Epub 2017 Aug 12.
Kashin-Beck disease (KBD) is a chronic, endemic osteochondropathy. Its etiopathogenesis is still obscure until now. Epidemiological observation has shown that low selenium play a crucial role in the pathogenesis of KBD. Extracellular signal-regulated kinases (ERKs) and C-Jun N-terminal kinase (JNK), members of the mitogen-activated protein kinase (MAPK) superfamily, play an important role in cell proliferation and differentiation. Nuclear factor-ĸB (NF-ĸB), an important signaling mediator for inflammatory and immune responses, is involved in the regulation of osteoclastogenesis. In the present study, we investigated the expression of ERK and JNK signal molecular, as well as nuclear factor-ĸB in the pathogenesis of Kashin-Beck disease, evaluated the effect of selenium on ERK signal pathway. The expression levels of ERK and JNK signal pathway, as well as nuclear factor-ĸB were investigated for 218 patients and 209 controls by immunoblot analysis in whole blood. Evaluated the effect of selenium on ERK signal pathway by NaSeO treatment. The protein levels of pRaf-1, pMek1/2 and pErk1/2 decreased significantly in KBD patients, p-JNK and NF-ĸB increased in KBD patients. Furthermore, NaSeO treatment improved the reduction of proteins in ERK signal pathway. These findings indicated that ERK and JNK signaling pathways, as well as the expression level of NF-κB signaling molecular are important contributor to the pathogenesis of KBD. Selenium stimulates the phosphorylation of the ERK signaling pathway.
大骨节病（KBD）是一种慢性地方性骨软骨病。其发病机制至今仍不清楚。流行病学观察表明，低硒在大骨节病的发病机制中起关键作用。细胞外信号调节激酶（ERKs）和C-Jun氨基末端激酶（JNK）是丝裂原活化蛋白激酶（MAPK）超家族的成员，在细胞增殖和分化中起重要作用。核因子-κB（NF-κB）是炎症和免疫反应的重要信号介质，参与破骨细胞生成的调节。在本研究中，我们研究了ERK和JNK信号分子以及核因子-κB在大骨节病发病机制中的表达，评估了硒对ERK信号通路的影响。通过免疫印迹分析检测了218例患者和209例对照全血中ERK和JNK信号通路以及核因子-κB的表达水平。通过亚硒酸钠处理评估硒对ERK信号通路的影响。大骨节病患者中pRaf-1、pMek1/2和pErk1/2的蛋白水平显著降低，p-JNK和NF-κB在大骨节病患者中升高。此外，亚硒酸钠处理改善了ERK信号通路中蛋白质的减少。这些发现表明，ERK和JNK信号通路以及NF-κB信号分子的表达水平是大骨节病发病机制的重要因素。硒刺激ERK信号通路的磷酸化。
