Alteration of m6A-Tagged RNA Profiles in Bone Originated from Periprosthetic Joint Infection

Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N-6-methyladenine (m(6)A) modification in PJI. Synovium, synovial fluid, sonication fluid and bone samples were collected intraoperatively from Staphylococcus aureus PJI and aseptic failure (AF) patients. The overall m(6)A level was detected by the m(6)A RNA methylation quantification kit, and the expression of m(6)A-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 m(6)A level between the PJI group and the AF group (PJI group had a higher overall m(6)A level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential m(6)A-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential m(6)A-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 m(6)A 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 m(6)A modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.

Automated summary

This study aimed to investigate the role of N-6-methyladenine (m(6)A) modification in periprosthetic joint infection (PJI). Samples were collected from PJI and aseptic failure patients, and m(6)A levels and expression of m(6)A-related genes were measured. Differential m(6)A-modified mRNAs were identified, and pathway analysis indicated the involvement of m(6)A modification in infection, immune response, bone metabolism, and cell death in PJI. This study demonstrated the significance of m(6)A modification as a potential therapeutic target for PJI.