Regulation Of 14-3-3 On Pyroptosis Of Dpscs

As preserving vital pulp tissue under controlled infection, the inflammatory vital pulp therapy (VIPT) is crucial for young permanent teeth. Inflammation impairs the capacity of dental pulp stem cells (DPSCs) and induce pyroptosis, hindering vital pulp preservation. Previous studies revealed 14-3-3 was upregulated in inflamed pulp tissues and facilitated nuclear-to-cytoplasmic translocation of FOXO3a. However, whether 14-3-3 could regulate DPSCs pyroptosis remains to be elucidated. Present study aims to investigate the regulatory mechanism of 14-3-3 in DPSCs pyroptosis via FOXO3a. Transcriptome sequencing and RT-qPCR evaluated 14-3-3 expression in inflamed pulp tissues and DPSCs. DPSCs pyroptosis was analyzed by YO-PRO-1/PI staining, Western Blot, immunofluorescence, and ELISA. 14-3-3ζ or 14-3-3θ was overexpressed in DPSCs and Co-IP was performed to investigate the regulation of 14-3-3 on pyroptosis via FOXO3a. Histological analysis assessed the effects of 14-3-3 inhibitor on VIPT of rat. 14-3-3ζ and 14-3-3θ was upregulated in inflamed pulp tissues and pyroptotic DPSCs. Overexpression of 14-3-3ζ or 14-3-3θ promoted DPSCs pyroptosis by facilitating FOXO3a nuclear-to-cytoplasmic translocation, thereby reducing FOXO3a mediated transcriptional repression of NLRP3. 14-3-3 inhibitor alleviated inflammatory responses in rat pulpitis. In inflamed pulp tissues and DPSCs, 14-3-3ζ and 14-3-3θ were upregulated. The function of 14-3-3/FOXO3a in regulating DPSCs pyroptosis maybe a potential therapeutic target for VIPT.