Inflammation‐Regeneration Axis of Dental Pulp Stem Cells: Wnt/NF‐κB Crosstalk

Evidence demonstrates context-dependent Wnt/NF-κB crosstalk in DPSC fate specification. Low-dose LPS (< 1 μg/mL) stimulates reparative responses through coordinated Wnt/NF-κB activation, whereas sustained high-dose exposure (> 1 μg/mL) suppresses Wnt signaling via NF-κB-driven DKK1 upregulation, attenuating differentiation capacity. While no direct evidence links Wnt/NF-κB crosstalk to DPSC self-renewal, both pathways independently maintain stemness. Critically, DPSCs and macrophages exhibit reciprocal regenerative interactions: DPSC-derived Wnt3a polarises macrophages toward the anti-inflammatory M2 phenotype, while M2-secreted Wnt7b enhances DPSC odontogenic differentiation by suppressing NF-κB expression. However, standardised inflammation models remain lacking, hindering comprehensive elucidation of context-dependent mechanisms. Developing such models would clarify how inflammation temporally and spatially influences regenerative outcomes across clinical scenarios.