FOXQ1–FGF10 axis attenuates inflammation in human dental pulp stem cells by suppressing NF-κB signaling

Abstract

The inflammatory response of human dental pulp stem cells (hDPSCs) plays a crucial role in the pathogenesis of pulpitis; however, the underlying regulatory mechanisms remain elusive. In this study, FOXQ1 was identified as a key transcriptional regulator that attenuates inflammation by suppressing NF-κB signaling through its downstream effector, FGF10. Temporal expression analysis revealed significant downregulation of FOXQ1 in LPS-stimulated hDPSCs, with maximum suppression observed at 24 h post-stimulation. FOXQ1 overexpression significantly decreased the expression of pro-inflammatory cytokines ( IL-1β, IL-6, and TNF-α ) while concurrently increasing the expression of anti-inflammatory mediators ( IL-4 and IL-10 ). Notably, FGF10 knockdown using siRNA abrogated the anti-inflammatory effects of FOXQ1 . Mechanistically, FOXQ1 upregulated FGF10 , resulting in decreased IKK and p65 phosphorylation, and impaired p65 nuclear translocation, thereby suppressing NF-κB activation. Functional rescue experiments confirmed that FGF10 silencing reversed FOXQ1 -mediated anti-inflammatory effects and restored NF-κB signaling. Collectively, these findings established the FOXQ1–FGF1 0–NF-κB axis as a novel regulatory pathway in dental pulp inflammation, highlighting its potential as a therapeutic target for managing pulpitis.