Regulated Cell Death In Osteoblast Induced By P. Gingivalis

This study aimed to investigate the mechanisms of regulated cell death (RCD) in osteoblasts during chronic apical periodontitis, focusing on the role of Porphyromonas gingivalis (P. gingivalis). Single-cell RNA sequencing (scRNA-seq) of human periapical tissues identified osteoblast heterogeneity. In vitro experiments, MG63 osteoblasts infected with P. gingivalis at varying multiplicities of infection (MOI) were used to assess viability (CCK-8), cytotoxicity (LDH), apoptosis (TUNEL, flow cytometry), ROS accumulation, and gene/protein expression (qRT-PCR, Western blot). Proteomic analysis and protein-protein interaction (PPI) networks explored molecular pathways. Immunofluorescence staining and Western blot further verified the mechanism of P. gingivalis regulating osteoblast RCD. The expression patterns of RCD-related genes changed in osteoblasts of human chronic apical periodontitis. High MOI (500–1000) of P. gingivalis promoted osteoblast apoptosis and pyroptosis while suppressing necroptosis and ferroptosis in vitro experiments. Proteomics identified 94 RCD-related proteins, with CDKN1A driving apoptosis via MAPK activation. P. gingivalis induces osteoblast death through RCD modulation, mediated by CDKN1A and p53/MAPK pathways. These findings elucidate mechanisms of bone resorption in apical periodontitis and suggest potential therapeutic targets.