School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China.
School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an, Shaanxi 710061, PR China; Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden.
Exp Cell Res. 2019 Jun 15;379(2):140-149. doi: 10.1016/j.yexcr.2019.04.001. Epub 2019 Apr 2.
To investigate the pathogenesis of Kashin-Beck disease (KBD), we compared the common signaling pathways in peripheral blood mononuclear cells (PBMCs) obtained from healthy juvenile and adults and KBD patients, and also from osteoarthritis (OA) patients. The PBMCs from 12 KBD and 12 healthy juvenile, and those from 20 adult KBD patients and 12 healthy donors were separately collected among the people living in the KBD endemic area. The patients were distinguished according to the national diagnosis criteria. Total RNAs were extracted for the determination of gene expressions by microarray analysis. Ingenuity Pathways Analysis (IPA) was employed to identify the signaling pathways significantly affected by juveniles' and adults' KBD, and OA. The expressions of NFκB-p65, cIAP2 and RANKL in the articular cartilage from both juvenile and adults were detected by immunohistochemistry. NF-κB signaling, apoptosis signaling, death receptor signaling and IL-6 signaling pathways were revealed to be the common affected signaling pathways in the juvenile and adult KBD and the OA. BIRC3 and EGR1 were identified as two common differentially expressed genes. The percentages of positive staining of NFκB-p65, cIAP2 and RANKL were reduced in adult KBD patients but significantly increased in juvenile KBD patients. NF-κB, one of the common signaling pathways between adult and juvenile KBD, was less prominent in the adult KBD patients.
为了探究大骨节病（KBD）的发病机制，我们比较了来自健康青少年和成人以及 KBD 患者和骨关节炎（OA）患者外周血单个核细胞（PBMC）中的常见信号通路。从 KBD 流行地区的人群中分别收集了 12 名 KBD 和 12 名健康青少年以及 20 名成人 KBD 患者和 12 名健康供体的 PBMC。根据国家诊断标准将患者区分开来。提取总 RNA 进行微阵列分析以确定基因表达。采用 IPA 分析鉴定受青少年和成人 KBD 和 OA 显著影响的信号通路。通过免疫组织化学检测关节软骨中 NFκB-p65、cIAP2 和 RANKL 的表达。揭示 NF-κB 信号、细胞凋亡信号、死亡受体信号和 IL-6 信号通路是青少年和成人 KBD 以及 OA 中常见的受影响信号通路。鉴定出 BIRC3 和 EGR1 是两个常见的差异表达基因。在成年 KBD 患者中 NFκB-p65、cIAP2 和 RANKL 的阳性染色百分比降低，但在青少年 KBD 患者中则显著增加。NF-κB 是成人和青少年 KBD 之间的共同信号通路之一，在成年 KBD 患者中则不明显。
