DDIT3 aggravates pulpitis by modulating M1 polarization through EGR1 in macrophages

Area of Science:

• Oral Biology
• Immunology
• Molecular Biology

Background:

• DNA damage-inducible transcript 3 (DDIT3) is a stress response gene involved in physiological and pathological processes.
• Macrophage polarization significantly impacts inflammatory responses, but DDIT3's role in pulpitis remains undefined.

Purpose of the Study:

• To investigate the effect of DDIT3 on pulpitis inflammation.
• To determine DDIT3's influence on macrophage polarization in the context of pulpitis.

Main Methods:

• Experimental pulpitis was induced in C57BL/6J mice.
• Histological analysis and assessment of macrophage polarization (M1/M2) were performed.
• In vitro studies utilized RAW264.7 cells and bone-marrow-derived macrophages to examine DDIT3's effects on polarization, including EGR1 knockdown.

Main Results:

• Pulpitis progression was observed histologically with dynamic DDIT3 expression.
• DDIT3 knockout mice exhibited reduced inflammation, fewer M1 macrophages, and more M2 macrophages compared to wild-type.
• DDIT3 promoted M1 polarization and inhibited M2 polarization in vitro, an effect reversed by EGR1 knockdown.

Conclusions:

• DDIT3 exacerbates pulpitis inflammation by regulating macrophage polarization.
• DDIT3 promotes M1 polarization by inhibiting early growth response 1 (EGR1).
• DDIT3 presents a novel therapeutic target for pulpitis treatment and future tissue regeneration strategies.