Setiwalidi Kaidiriye, Fu Jialei, Hei He, Nuer Shaniya, Zhang Feiyu, Chen Sijie, Liu Yanli, Chen Feihong, Li Shujin, Wang Chaowei, Wu Yifan, Gong Yi, Hu Minhan, Huang Ruitian, Liu Junyi, Zhang Tianxiao, Ning Yujie, Zhao Hongmou, Guo Xiong, Wang Xi
School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, Xi'an, China.
Department of Occupational and Environmental Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Front Genet. 2022 Dec 14;13:1053685. doi: 10.3389/fgene.2022.1053685. eCollection 2022.
The purpose of this study was clarify the relationship between the differential expression of cyclins CCNB1 and CCNG1 and chondrocyte damage in Kashin-Beck disease. Systematic review and high-throughput sequencing of chondrocytes derived from Kashin-Beck disease patients were combined to identify the differentially expressed cyclins and cyclin-dependent kinase genes. In parallel, weaned SD rats were treated with low selenium for 4 weeks and then T-2 toxin for 4 weeks. Knee cartilage was collected to harvest chondrocytes for gene expression profiling. Finally, the protein expression levels of CCNB1 and CCNG1 were verified in knee cartilage tissue of Kashin-Beck disease patients and normal controls by immunohistochemical staining. The systematic review found 52 cartilage disease-related cyclins and cyclin-dependent kinase genes, 23 of which were coexpressed in Kashin-Beck disease, including 15 upregulated and 8 downregulated genes. Under the intervention of a low selenium diet and T-2 toxin exposure, CCNB1 (FC = 0.36) and CCNG1 (FC = 0.73) showed a downward expression trend in rat articular cartilage. Furthermore, compared to normal controls, CCNB1 protein in Kashin-Beck disease articular cartilage was 71.98% and 66.27% downregulated in the superficial and middle zones, respectively, and 12.06% upregulated in the deep zone. CCNG1 protein was 45.66% downregulated in the superficial zone and 12.19% and 9.13% upregulated in the middle and deep zones, respectively. The differential expression of cyclins CCNB1 and CCNG1 may be related to articular cartilage damage in Kashin-Beck disease.
本研究旨在阐明细胞周期蛋白CCNB1和CCNG1的差异表达与大骨节病软骨细胞损伤之间的关系。我们将大骨节病患者软骨细胞的系统评价与高通量测序相结合，以鉴定差异表达的细胞周期蛋白和细胞周期蛋白依赖性激酶基因。同时，对断乳后的SD大鼠进行4周低硒处理，然后进行4周T-2毒素处理。收集膝关节软骨以获取软骨细胞进行基因表达谱分析。最后，通过免疫组织化学染色验证大骨节病患者和正常对照者膝关节软骨组织中CCNB1和CCNG1的蛋白表达水平。系统评价发现52个与软骨疾病相关的细胞周期蛋白和细胞周期蛋白依赖性激酶基因，其中23个在大骨节病中共同表达，包括15个上调基因和8个下调基因。在低硒饮食和T-2毒素暴露的干预下，CCNB1（FC = 0.36）和CCNG1（FC = 0.73）在大鼠关节软骨中呈下调表达趋势。此外，与正常对照相比，大骨节病关节软骨中CCNB1蛋白在表层和中层分别下调了71.98%和66.27%，在深层上调了12.06%。CCNG1蛋白在表层下调了45.66%，在中层和深层分别上调了12.19%和9.13%。细胞周期蛋白CCNB1和CCNG1的差异表达可能与大骨节病的关节软骨损伤有关。
