EZH2-Mediated Epigenetic Modifications Induce Pyroptosis in Dental Pulp Endothelial Cells via Activation of NLRP6 Inflammasome During Pulpitis Development.

OBJECTIVES

Recent studies suggest that alleviating pyroptosis may be an effective strategy for treating inflammation. This research explores the changes in cellular composition and pyroptotic pathways in dental pulp tissue during pulpitis and preliminarily validates the regulatory role of EZH2 in lipopolysaccharide (LPS)-induced pyroptosis of vascular endothelial cells (ECs) via NLRP6, aiming to provide a theoretical foundation for understanding pulpitis mechanisms.

METHODS

Bioinformatics analysis of public single-cell RNA sequencing (scRNA-seq) and microarray data, together with RNA-seq of EZH2fl/fl;Tie2-Cre+/- pulp tissue, was performed to investigate the involvement of ECs and pyroptosis in pulpitis. Functional validation was conducted using an EZH2-inhibited inflammatory model and an NLRP6 knockdown model.

RESULTS

Bioinformatics analysis revealed a strong association between pulpitis and EC pyroptosis. RNA-seq further demonstrated that EZH2 deficiency was associated with enhanced pyroptotic responses in ECs. In vitro, EZH2 inhibition or NLRP6 knockdown markedly attenuated LPS-induced inflammasome activation and pyroptosis in EOMA cells. This illustrates that the EZH2/NLRP6 axis plays a critical regulatory role in EC pyroptosis and suggests its potential as a therapeutic target in pulpitis.

CONCLUSIONS

In summary, this study establishes ECs as key regulators in pulpitis inflammation, highlighting EZH2's role in modulating NLRP6 and the potential mechanism of pyroptosis in ECs.