Screening and biological function analysis of inflammation-related circRNAs in synovial tissue of patients with primary knee osteoarthritis

doi:10.12307/2022.668

Abstract

Abstract: BACKGROUND: Primary knee osteoarthritis is one of the most common chronic diseases among the elderly, which brings a heavy burden on society and families. Current clinical treatments only focus on surgeries such as total knee replacement, but it is difficult to prevent cartilage tissue degeneration at an early stage. The formation mechanism of knee osteoarthritis, especially the influence of inflammation in disease progression, has been reported to some extent, but its specific mechanism is still unclear.
OBJECTIVE: To investigate the differentially expressed circRNA sites of primary knee osteoarthritis and rheumatoid arthritis and their effects on the pathogenesis of the disease.
METHODS: In this study, we collected the synovial tissues from eight patients with primary knee osteoarthritis and two patients with rheumatoid arthritis (control group). The expression profile of circRNAs in the tissue was detected by RNA-seq technique, trying to find the differentially expressed genes and key biological function pathways.
RESULTS AND CONCLUSION: Compared with patients with rheumatoid arthritis, 185 differentially expressed circRNAs were detected in patients with knee osteoarthritis, of which 14 were up-regulated and 171 were down-regulated. Through the pathway enrichment and functional annotation of these target genes, a variety of enrichment pathways were identified, including protein H3-K36 dimethylation, glycosphingolipid biosynthesis process, and positive regulation of Toll-like receptor 9 signaling pathway. Based on the above sequencing results, a circRNA-miRNA interaction network was created, contributing to understanding the effect of differentially expressed circRNAs. In this study, we determined the differential expression of inflammation-related circRNAs in synovial tissue and the control group. These differentially expressed transcripts may elucidate the effect of circRNA and its relationship network in synovial tissue on the progression of osteoarthritis. Findings from this study will be helpful to explore the pathogenesis and key therapeutic targets of osteoarthritis.

Key words: osteoarthritis, rheumatoid arthritis, circRNA, inflammation, synovial tissue, RNA-seq

CLC Number:

Qiao Linghui, Yuan Tao, Han Jie, Wang Guancheng, Gu Yanglin. Screening and biological function analysis of inflammation-related circRNAs in synovial tissue of patients with primary knee osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(23): 3683-3690.

Figures/Tables 6

从图上可以看出，在生物过程(Biological Process)层面，骨关节炎组患者滑膜组织差异表达的circRNA主要富集于蛋白 H3-K36 二甲基化、鞘糖脂生物合成过程、Toll样受体9信号通路的正调控、核糖体蛋白导入细胞核、GTP酶活性的调节等过程。在细胞成分(cellular component)层面，骨关节炎组患者滑膜组织差异表达的circRNA主要富集于细胞膜、高尔基体、细胞内膜结合的细胞器、细胞连接、早期内体膜等细胞组分中。在分子功能(molecular_function)层面，钾离子和钠离子逆向转运蛋白活性、内质网管状网络、激活信号协整器 1 复合物、转移酶活性、非跨膜蛋白酪氨酸磷酸酶活性等均在骨关节炎组中有明显差异表达。 2.4 骨关节炎组和类风湿性关节炎组滑膜组织circRNA差异表达KEGG分析 KEGG(Kyoto Encyclopedia of Genes and Genomes)是由日本京都大学和东京大学联合开发的数据库，是系统分析基因功能、联系基因组信息和功能信息的知识库，可以用来查询代谢途径、酶(或编码酶的基因)、代谢产物等，也可以通过BLAST比对查询未知序列的代谢途径信息(www.genome.jp/kegg)。骨关节炎组和类风湿性关节炎组滑膜组织差异表达的circRNA主要参与了肾素分泌、长期增益效应、人类免疫缺陷病毒1型感染、硒化合物代谢、糖胺聚糖生物合成——硫酸软骨素/硫酸皮肤素、血管内皮生长因子信号通路、长期抑郁、cGMP-PKG信号通路、催乳素信号通路等，见图6A。KEGG分析进一步揭示富集circRNA在已知通路中的表达情况。图6B为血管内皮生长因子信号通路(VEGF signaling pathway)富集分析图，黄色代表注释到某个ko节点的显著差异表达基因既有上调也有下调，实心箭头表示生化反应的方向，虚线箭头连接其他的相关代谢途径。"

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