BACKGROUND: The association between periodontitis (PT) and rheumatoid arthritis (RA) is well-established
however, the molecular mechanisms underlying this relationship remain poorly understood. This study aims to delineate shared genetic and molecular features between PT and RA to uncover potential common pathways involved in their pathogenesis. METHODS: Gene expression data sets for PT and RA were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and co-expressed gene modules were identified using weighted gene co-expression network analysis (WGCNA) and the DESeq2 package. Enrichment analyses, including KEGG and Gene Ontology (GO) pathways, as well as immune cell infiltration profiling, were performed to explore shared biological pathways. A protein-protein interaction (PPI) network was constructed to pinpoint key genes linking PT and RA. Functional assays were conducted by overexpressing the identified core gene, PTPRC, in MH7A cells via lentiviral transfection, followed by cell viability (CCK-8), migration, and invasion assays. In addition, transcription factor enrichment and connectivity map (cMAP) analyses were employed to identify common transcriptional regulators and potential therapeutic targets for both conditions. RESULTS: WGCNA and DESeq2 analyses revealed 154 shared DEGs between PT and RA, predominantly enriched in immune and inflammatory response pathways. PTPRC emerged as a pivotal shared gene, exhibiting significantly higher expression in PT patients compared to controls. In vitro assays confirmed that PTPRC overexpression enhanced fibroblast proliferation, migration, and invasion. Furthermore, transcription factor enrichment analysis and cMAP identified overlapping transcriptional regulators and potential pharmacological agents for both diseases. CONCLUSIONS: This study provides novel insights into shared gene expression profiles and molecular mechanisms linking PT and RA, identifying PTPRC as a potential key regulator. These findings suggest that targeting PTPRC could offer therapeutic opportunities for RA driven by PT.