EZH2 knockout in mice activates STAT3 signalling via STAT3 methylation and modulates ferroptosis in pulpitis-affected dental pulp vascular endothelial cells: A laboratory investigation.

Abstract

Aim: Recent findings suggest that mitigating ferroptosis could serve as an effective strategy for treating inflammation. This study aimed to investigate the role that the enhancer of zeste homologue 2 (EZH2) mediated the signal transducer and activator of transcription 3 (stat3) methylation plays in the modulation of ferroptosis in pulpitis. The study results offer potential advancements in the therapeutic approaches for pulpitis and provide new insights and strategies for managing this condition.

Methodology: Bioinformatics analysis combined with methylation capture sequencing of EZH2^fl/flCre^+/- pulp tissue was used to explore the association between pulpitis and ferroptosis. In this study, we used an EZH2 knockout model prepared through lentiviral transduction and an LPS-induced inflammatory model of endometrial mesenchymal stromal cells to confirm the role that the EZH2/STAT3 axis plays in ferroptosis.

Results: Bioinformatics analysis identified a link between pulpitis and DNA methylation. Methylation sequencing further revealed the association of methylation with ferroptosis and the regulation of STAT3 methylation by EZH2. In vitro, lipopolysaccharide (LPS) stimulation induced ferroptosis, whereas EZH2 disruption suppressed STAT3 expression but increased Glutathione Peroxidase 4 (GPX4) expression, leading to the escalation of oxidative stress and exacerbation of ferroptosis. This illustrates the complex interactions between methylation, ferroptosis and oral inflammation, highlighting potential therapeutic targets.

Conclusions: Overall, pulpitis plays a crucial role in EZH2-mediated STAT3 methylation and activates ferroptosis by regulating GPX4 expression. This study provides new insights and strategies for treatment and advances our understanding of the pathogenesis of pulpitis.