Complement C5a receptor antagonist in the treatment of experimental periodontitis in mice

Periodontitis arises from dysbiosis of the oral microbiome and excessive host immune responses, with the C5a–C5aR axis playing a key role in destructive inflammation. This study evaluated the efficacy of the C5aR antagonist W54011 in treating experimental periodontitis in mice. A ligature‐induced periodontitis model combined with localized Porphyromonas gingivalis lipopolysaccharide (LPS) injection was established to mimic human disease progression. Periodontal inflammation was assessed by measuring TNF‐α and IL‐6 levels via enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction, while C5aR expression was analyzed by western blot and immunohistochemistry. Micro‐computed tomography (micro‐CT) quantified alveolar bone resorption. Results showed that TNF‐α, IL‐6, and C5aR expression was significantly upregulated in periodontitis‐affected mice compared to healthy controls. W54011 treatment effectively suppressed these inflammatory mediators and reduced C5aR expression. Furthermore, micro‐CT revealed that W54011 significantly attenuated bone loss, preserving periodontal architecture. These findings demonstrate that pharmacological blockade of C5aR with W54011 attenuates periodontal inflammation and reduces alveolar bone destruction, suggesting its potential as a novel host‐modulation therapy for periodontitis. The study provides mechanistic insights into C5a–C5aR signaling in periodontitis pathogenesis while proposing a promising therapeutic strategy.