Wang Sen, Wang Yuanji, Li Xingyu, Yuan Linlin, Guo Xiong, Lammi Mikko J
School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Pharmacy, The First Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China.
Front Genet. 2023 May 23;14:1169417. doi: 10.3389/fgene.2023.1169417. eCollection 2023.
This study aimed to investigate the roles of accessible chromatin in understanding the different pathogeneses between Kashin-Beck disease (KBD) and primary osteoarthritis (OA). Articular cartilages of KBD and OA patients were collected, and after tissue digestion, primary chondrocytes were cultured . Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) was performed to compare the accessible chromatin differences of chondrocytes between KBD and OA groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were executed for the promoter genes. Then, the IntAct online database was used to generate networks of significant genes. Finally, we overlapped the analysis of differentially accessible region (DAR)-associated genes and differentially expressed genes (DEGs) obtained from whole-genomic microarray. We obtained 2,751 total DARs, which contained 1,985 loss and 856 gain DARs and belonged to 11 location distributions. We obtained 218 motifs associated with loss DARs, 71 motifs associated with gain DARs, 30 motif enrichments of loss DARs, and 30 motif enrichments of gain DARs. In total, 1,749 genes are associated with loss DARs, and 826 genes are associated with gain DARs. Among them, 210 promoter genes are associated with loss DARs, and 112 promoter genes are associated with gain DARs. We obtained 15 terms of GO enrichment and 5 terms of KEGG pathway enrichment from loss DAR promoter genes, and 15 terms of GO enrichment and 3 terms of KEGG pathway enrichment from gain DAR promoter genes. We obtained CAPN6 and other 2 overlap genes from loss DARs-vs-down DEGs, AMOTL1 from gain DARs-vs-down DEGs, EBF3 and other 12 overlap genes from loss DARs-vs-up DEGs, and ADARB1 and other 10 overlap genes from 101 gain DARs-vs-up DEGs. These overlap genes were built into 4 gene interaction networks. and were the overlapped genes from the DAR-associated genes and DEGs. These genes were associated with the abnormal chondrocyte function, which may play crucial roles in different processes between KBD and OA in the way of accessible chromatin.
本研究旨在探讨可及染色质在理解大骨节病（KBD）和原发性骨关节炎（OA）不同发病机制中的作用。收集KBD和OA患者的关节软骨，经组织消化后培养原代软骨细胞。进行转座酶可及染色质高通量测序分析（ATAC-seq），以比较KBD组和OA组软骨细胞可及染色质的差异。对启动子基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。然后，使用IntAct在线数据库生成重要基因的网络。最后，我们将差异可及区域（DAR）相关基因分析与全基因组微阵列获得的差异表达基因（DEG）进行了重叠分析。我们共获得2751个DAR，其中包含1985个缺失DAR和856个增加DAR，属于11种位置分布。我们获得了与缺失DAR相关的218个基序、与增加DAR相关的71个基序、缺失DAR的30个基序富集和增加DAR的30个基序富集。共有1749个基因与缺失DAR相关，826个基因与增加DAR相关。其中，210个启动子基因与缺失DAR相关，112个启动子基因与增加DAR相关。我们从缺失DAR启动子基因中获得15个GO富集项和5个KEGG通路富集项，从增加DAR启动子基因中获得15个GO富集项和3个KEGG通路富集项。我们从缺失DAR与下调DEG中获得钙蛋白酶6（CAPN6）和其他2个重叠基因，从增加DAR与下调DEG中获得血管生成素样蛋白1（AMOTL1），从缺失DAR与上调DEG中获得早期B细胞因子3（EBF3）和其他12个重叠基因，从101个增加DAR与上调DEG中获得腺苷脱氨酶RNA特异性B1（ADARB1）和其他10个重叠基因。这些重叠基因构建成4个基因相互作用网络。 和 是DAR相关基因和DEG的重叠基因。这些基因与软骨细胞功能异常相关，可能通过可及染色质的方式在KBD和OA的不同过程中发挥关键作用。
