PMAIP1 mediates endoplasmic reticulum stress in human dental pulp stem cells during pulpitis pathogenesis

Area of Science:

• Oral Biology
• Molecular Pathology
• Biomedical Research

Background:

• Pulpitis, or dental pulp inflammation, significantly impacts oral health.
• The molecular mechanisms underlying pulpitis remain poorly understood.
• This study investigates the role of endoplasmic reticulum (ER) stress in pulpitis pathogenesis.

Purpose of the Study:

• To investigate the role of ER stress in pulpitis.
• To identify key molecular players in ER stress-induced pulpitis.
• To evaluate the therapeutic potential of targeting ER stress in pulpitis.

Main Methods:

• Examined ER stress markers (BiP, CHOP) in human pulpitis specimens and lipopolysaccharide (LPS)-treated human dental pulp stem cells (hDPSCs).
• Performed transcriptomic analysis of public datasets to identify ER stress-related differentially expressed genes (DEGs).
• Evaluated the therapeutic efficacy of 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, in vitro and in vivo pulpitis models.

Main Results:

• Elevated BiP and CHOP expression confirmed ER stress in pulpitis and LPS-treated hDPSCs.
• Bioinformatic analysis identified 19 ER stress-related DEGs, with PMAIP1 as a central regulator.
• 4-PBA treatment attenuated LPS-induced ER stress and inflammatory responses in hDPSCs and experimental pulpitis.

Conclusions:

• Endoplasmic reticulum stress is a critical mediator in pulpitis pathogenesis.
• PMAIP1 is identified as a key regulatory hub in ER stress-related pulpitis.
• Targeting ER stress with 4-PBA represents a promising therapeutic strategy for pulpitis.