Cai Yuanqing, Chen Xiaoqing, Huang Changyu, Chen Yang, Zhang Chaofan, Huang Zida, Zhang Wenming, Tang Yusen, Fang Xinyu
Department of Orthopaedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
Department of Orthopaedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
J Clin Med. 2023 Apr 14;12(8):2863. doi: 10.3390/jcm12082863.
Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N-methyladenine (mA) modification in PJI. Synovium, synovial fluid, sonication fluid and bone samples were collected intraoperatively from PJI and aseptic failure (AF) patients. The overall mA level was detected by the mA RNA methylation quantification kit, and the expression of mA-related genes was quantified by real-time PCR and Western blot. Finally, an epitranscriptomic microarray and bioinformatics analysis were performed. We showed that there was a significant difference in overall mA level between the PJI group and the AF group (PJI group had a higher overall mA level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential mA-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential mA-modified mRNAs were significantly enriched in the NOD-like receptor signaling pathway, Th17 cell differentiation and the IL-17 signaling pathway, which indicates that the mA modification might be involved in the processes of infection and immune response, bone metabolism and programmed cell death in PJI. In summary, the present work demonstrated that mA modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.
人工关节周围感染(PJI)是一种严重的并发症。本研究旨在揭开PJI中N-甲基腺嘌呤(mA)修饰的面纱。术中从PJI和无菌性失败(AF)患者中采集滑膜、滑液、超声处理液和骨样本。使用mA RNA甲基化定量试剂盒检测总体mA水平,并通过实时PCR和蛋白质免疫印迹法对与mA相关的基因表达进行定量。最后,进行了表观转录组微阵列和生物信息学分析。我们发现PJI组和AF组之间的总体mA水平存在显著差异(PJI组的总体mA水平更高)。PJI组中METTL3的表达水平高于AF组。有2802个差异mA修饰的mRNA。京都基因与基因组百科全书(KEGG)分析表明,差异mA修饰的mRNA在NOD样受体信号通路、Th17细胞分化和IL-17信号通路中显著富集,这表明mA修饰可能参与了PJI中的感染和免疫反应、骨代谢及程序性细胞死亡过程。总之,目前的研究表明mA修饰在PJI中发挥作用,可能是制定有效治疗策略的治疗靶点。