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

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.