Lpar3-mediated macrophage polarization promotes inflammatory tooth extraction socket healing and alveolar bone regeneration

Delayed healing of extraction sockets under inflammatory conditions, such as periodontitis, remains a common clinical challenge. Persistent inflammation and dysregulated immune responses are increasingly recognized as key factors impairing alveolar bone regeneration; however, the underlying immunoregulatory mechanisms remain incompletely understood. An inflammatory tooth extraction model was established in mice. Macrophage polarization in healing sockets was analyzed by immunofluorescence and flow cytometry, and LPAR3/Lpar3 expression was examined in mouse extraction socket tissues and human alveolar bone debris collected from healing sites using qRT-PCR. In vitro , RAW264.7 macrophages were treated with lysophosphatidic acid (LPA) or the LPAR3 agonist OMPT to assess M1/M2 polarization, and macrophage-conditioned media were applied to evaluate osteogenic differentiation of bone marrow stromal cells (BMSCs). In vivo , OMPT was locally administered into inflammatory tooth extraction sockets, and alveolar bone regeneration was evaluated by micro-computed tomography and histological analyses. M2 macrophage polarization was significantly impaired in inflammatory tooth extraction sockets, accompanied by marked downregulation of LPAR3/Lpar3 expression. In vitro , LPA promoted macrophage M2 polarization in a Lpar3-dependent manner, and activation of Lpar3 enhanced the pro-osteogenic effects of macrophages on BMSCs. In vivo , local activation of Lpar3 restored the M1/M2 balance and significantly improved alveolar bone regeneration in inflammatory sockets. These findings demonstrate that Lpar3-mediated macrophage polarization plays a critical role in inflammatory tooth extraction socket healing. Targeting the LPA–Lpar3 axis may represent a promising immunoregulatory strategy to enhance alveolar bone regeneration following tooth extraction under inflammatory conditions. • Inflammatory tooth extraction sockets exhibit impaired M2 macrophage polarization. • LPAR3 expression is downregulated during inflammatory socket healing. • LPA promotes macrophage M2 polarization via LPAR3 signaling. • Local activation of LPAR3 enhances bone regeneration after tooth extraction.