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Alteration of m6A-Tagged RNA Profiles in Bone Originated from Periprosthetic Joint Infection
Yuanqing Cai1,2,3,4, Xiaoqing Chen5, Changyu Huang1,2
1Department of Orthopaedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
Abstract:
Periprosthetic joint infection (PJI) is a devastating complication. This study aimed to unravel the veil of the N6-methyladenine (m6A) 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 m6A level was detected by the m6A RNA methylation quantification kit, and the expression of m6A-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 m6A level between the PJI group and the AF group (PJI group had a higher overall m6A level). The expression level of METTL3 was higher in the PJI group than that in the AF group. There were 2802 differential m6A-modified mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differential m6A-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 m6A 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 m6A modification plays a role in PJI and might be a therapeutic target for developing effective treatment strategies.
Insights
N6-methyladenine (m6A) RNA modification is elevated in periprosthetic joint infection (PJI). This epigenetic change impacts immune responses and bone metabolism, suggesting m6A as a potential therapeutic target for PJI treatment.
Area of Science:
- Molecular Biology
- Immunology
- Orthopedic Surgery
Background:
- Periprosthetic joint infection (PJI) is a severe complication following joint replacement surgery.
- Understanding the molecular mechanisms underlying PJI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of N6-methyladenine (m6A) RNA modification in the pathogenesis of PJI.
- To identify potential therapeutic targets for PJI based on m6A modification.
Main Methods:
- Collected intraoperative samples (synovium, synovial fluid, sonication fluid, bone) from Staphylococcus aureus PJI and aseptic failure (AF) patients.
- Quantified overall m6A levels using an RNA methylation kit.
- Assessed m6A-related gene expression via real-time PCR and Western blot.
- Performed epitranscriptomic microarray and bioinformatics analysis.
Main Results:
- Overall m6A levels were significantly higher in the PJI group compared to the AF group.
- The expression of METTL3, an m6A-related gene, was elevated in PJI patients.
- Identified 2802 differentially m6A-modified mRNAs.
- Bioinformatics analysis revealed enrichment in pathways related to immune response (NOD-like receptor, Th17 cell differentiation, IL-17 signaling), bone metabolism, and programmed cell death.
Conclusions:
- m6A RNA modification plays a significant role in the pathophysiology of PJI.
- The identified m6A-modified genes and pathways offer potential targets for novel therapeutic strategies against PJI.
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