Advances in the role of specialized pro-resolving mediators in periodontitis.

Periodontitis is a chronic inflammatory disease driven by dysregulated host-microbial interactions and failure of endogenous inflammation resolution, leading to progressive destruction of periodontal tissues. Increasing evidence indicates that inflammation resolution is an active, tightly regulated biological program governed by specialized pro-resolving mediators (SPMs), including resolvins, lipoxins, protectins, and maresins. Unlike conventional anti-inflammatory agents, SPMs do not suppress host defense but instead actively terminate inflammation and promote tissue regeneration. Mechanistically, SPMs signal through specific G protein-coupled receptors to inhibit neutrophil recruitment, enhance macrophage efferocytosis, and promote M2 macrophage polarization. They also suppress pro-inflammatory signaling pathways such as NF-κB and NLRP3 inflammasome activation, while restoring immune balance by modulating Treg/Th17 responses. Importantly, SPMs regulate periodontal bone homeostasis by correcting the RANKL/OPG imbalance and supporting osteogenic differentiation of periodontal ligament cells. This review summarizes the biosynthesis, receptor-mediated signaling, and functional roles of SPMs in periodontitis, highlighting their may connect inflammation resolution and tissue regeneration.