• ATF3 is downregulated in inflamed pulp tissues, and its overexpression reduces pulp necrosis and pro-inflammatory cytokine levels.
• ATF3 positively regulates WNT4 transcription by binding to its promoter, promoting M2 macrophage polarization while suppressing M1 markers.
• The ATF3/WNT4 axis enhances osteogenic differentiation of human dental pulp stem cells, suggesting a dual role in inflammation resolution and tissue repair.
• ATF3 emerges as a promising therapeutic target for pulpitis treatment, offering a novel strategy to modulate immune responses and promote pulp regeneration.