Transcriptomic Analysis Reveals PACS1 as a Potential Shared Candidate Biomarker for Apical Periodontitis and...

Apical periodontitis (AP), a localized inflammatory bone disease, and osteoporosis (OP), a systemic metabolic bone disorder, are both characterized by chronic inflammation and dysregulated bone metabolism, yet the molecular mechanisms underlying their association remain unclear. This study aimed to identify shared biomarkers and pathogenic pathways linking AP and OP. Gene expression datasets for AP and OP were obtained from the Gene Expression Omnibus database, and shared differentially expressed genes were identified and analyzed using functional enrichment, Gene set enrichment analysis (GSEA), Gene set variation analysis GSVA, and single-sample gene set enrichment analysis (ssGSEA)-based immune infiltration approaches. A random forest model was applied to prioritize candidate genes, followed by validation using single-cell RNA sequencing datasets, clinical samples, and in vitro assays. Forty-three shared differentially expressed genes were identified, among which FAM87B, ASCL2, and PACS1 were prioritized as candidate genes. PACS1 showed consistent upregulation in both AP and OP and was further validated in clinical samples. Integrated analyses suggested that shared molecular alterations were associated with NF-κB signaling and immune-metabolic dysregulation, while single-cell analysis supported PACS1 expression in cell subsets involved in inflammatory bone remodeling. Functionally, PACS1 knockdown promoted osteoblast differentiation, accompanied by increased ALP, RUNX2, and OPN expression. These findings suggest that PACS1 may serve as a shared candidate biomarker linking AP and OP and provide insight into immune-bone crosstalk in inflammatory bone loss.