P53 Alleviates Periodontitis By Suppressing Osteoclastogenesis Via Foxo Signaling Pathway

Alveolar bone resorption is the hallmark clinical feature of periodontitis, inhibiting alveolar bone resorption constitutes the primary therapeutic strategy for periodontitis treatment.The objective of this study is to demonstrate that P53 activation attenuates periodontitis progression by suppressing osteoclastogenesis through negative regulation of FOXO signaling pathway, thereby providing novel therapeutic insights for future periodontal disease management. 1.Single-cell RNA sequencing and transcriptomic profiling were used to delineate the correlation between P53 activation and periodontal disease progression, with particular emphasis on its regulatory mechanism in macrophage-osteoclast differentiation; 2.The ligature-induced periodontitis murine model was used to varify the impact of P53 on alveolar bone resorption and osteoclastogenesis dynamics; 3.In vitro osteoclastogenesis assays were conducted to investigate the regulatory effects of P53 modulation on macrophage-derived osteoclast differentiation. 1.Single-cell RNA sequencing revealed pronounced activation of P53 signaling way and upregulated osteoclastogenic potential in macrophage derived from human inflamed periodontal tissues; 2.In vivo studies demonstrated that P53 activation attenuates alveolar bone resorption in murine periodontitis models through suppression of osteoclast precursor differentiation, while in vitro mechanistic investigations revealed that P53 activation significantly inhibits RANKL-induced osteoclastogenesis;3.Transcriptomic profiling delineated that P53-mediated anti-osteoclastic effects were associated with downregulation of the FOXO signaling axis. Activation of P53 exerts inhibitory effects on alveolar bone resorption through negative regulation of FOXO signaling axis, thereby establishing a mechanistic foundation for developing precision-targeted therapeutic strategies against periodontitis.