IGSF10 Attenuates Periodontitis-Induced Bone Resorption Via Anti-Inflammatory Mechanisms

To investigate the role of IGSF10 in mitigating inflammation-driven alveolar bone loss and its underlying regulatory mechanisms. In vivo: IGSF10-knockout (KO) and wild-type (WT) C57BL/6 mice (male, 8 weeks old) were subjected to LPS-induced experimental periodontitis under ethics committee approval. Alveolar bone morphology was assessed by micro-CT, while histopathological analysis (H&E staining), osteoclast activity (TRAP staining), and inflammatory markers (IL-1B immunohistochemistry) were evaluated. Recombinant IGSF10 was locally administered to both KO and WT mice with periodontitis. In vitro: Human periodontal ligament fibroblasts (PDLCs) were stimulated with LPS and treated with recombinant IGSF10. RNA sequencing and pathway enrichment analysis identified key signaling networks. Cytokine levels, STAT1 activation, and macrophage polarization were analyzed via ELISA, Western blot, and flow cytometry. Statistical analysis was performed using one-way ANOVA. IGSF10 expression was significantly upregulated in inflamed periodontal tissues and LPS-stimulated PDLCs. Genetic ablation of IGSF10 exacerbated alveolar bone resorption and osteoclast activity in mice, while local administration of recombinant IGSF10 not only rescued bone loss in KO mice but also demonstrated therapeutic efficacy in WT periodontitis models by reducing bone resorption and inflammatory infiltration. Mechanistically, IGSF10 suppressed pro-inflammatory cytokine production and enhanced anti-inflammatory factor expression in PDLCs through STAT1 pathway activation, while promoting a shift toward M2 macrophage polarization. IGSF10 protects against periodontitis-induced alveolar bone loss by modulating STAT1-dependent anti-inflammatory signaling and immune cell reprogramming, highlighting its therapeutic potential in inflammatory bone disorders.