School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases in National Health Commission of PR of China, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
The Institute of Endemic Diseases, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Biol Trace Elem Res. 2021 Mar;199(3):944-954. doi: 10.1007/s12011-020-02237-1. Epub 2020 Jun 26.
Recent evidence suggests a role of type II collagen in Kashin-Beck disease (KBD) degeneration. We aimed to assess the abnormal expression of heat shock protein 47 (HSP47) which is associated with a decrease in type II collagen and an increase in cartilage degradation in KBD. Hand phalange cartilages were collected from KBD and healthy children. Rats were administered with T-2 toxin under the selenium (Se)-deficient diet. ATDC5 cells were seeded on bone matrix gelatin to construct engineered cartilaginous tissue. C28/I2 and ATDC5 cells and engineered tissue were exposed to different concentrations of T-2 toxin with or without Se. Cartilage degeneration was determined through histological evaluation. The distribution and expression of type II collagen and HSP47 were investigated through immunohistochemistry, western blotting, and real-time PCR. KBD cartilages showed increased chondronecrosis and extracellular matrix degradation in deep zone with decreased type II collagen and HSP47 expression. The low-Se + T-2 toxin animal group showed a significantly lower type II collagen expression along with decreased HSP47 expression. Decreased type II collagen and HSP47 in C28/I2 and ATDC5 cells induced by T-2 toxin showed a dose-dependent manner. Hyaline-like cartilage with zonal layers was developed in engineered cartilaginous tissues, with decreased type II collagen and HSP47 expression found in T-2 toxin-treated group. Se-supplementation partially antagonized the inhibitory effects of T-2 toxin in chondrocytes and cartilages. HSP47 plays a role in the degenerative changes of KBD and associated with T-2 toxin-induced decreased type II collagen expression, further promoting matrix degradation.
最近的证据表明，Ⅱ型胶原在大骨节病（KBD）退变中起作用。我们旨在评估热休克蛋白 47（HSP47）的异常表达，其与Ⅱ型胶原减少和软骨降解增加有关。收集 KBD 儿童和健康儿童的手指软骨。在缺硒（Se）饮食下给大鼠给予 T-2 毒素。将 ATDC5 细胞接种在骨基质明胶上，构建工程化软骨组织。将 C28/I2 和 ATDC5 细胞和工程化组织暴露于不同浓度的 T-2 毒素，有或没有 Se。通过组织学评估确定软骨退变。通过免疫组织化学、Western blot 和实时 PCR 研究Ⅱ型胶原和 HSP47 的分布和表达。KBD 软骨显示深层区软骨坏死和细胞外基质降解增加，Ⅱ型胶原和 HSP47 表达减少。低 Se+T-2 毒素动物组表现出明显较低的Ⅱ型胶原表达，同时 HSP47 表达减少。T-2 毒素诱导的 C28/I2 和 ATDC5 细胞中Ⅱ型胶原和 HSP47 的减少呈剂量依赖性。工程化软骨组织中形成具有层状带的透明软骨，T-2 毒素处理组中发现Ⅱ型胶原和 HSP47 表达减少。Se 补充部分拮抗了 T-2 毒素对软骨细胞和软骨的抑制作用。HSP47 在 KBD 的退行性变化中起作用，并与 T-2 毒素诱导的Ⅱ型胶原表达减少有关，进一步促进基质降解。
