Research indicates that M1 macrophages secrete various inflammatory cytokines, such as IL-6, IL-1, TNF-α, and prostaglandin E2 (PGE2), which stimulate osteoclast differentiation and activation, thereby contributing to bone resorption.46 Additionally, M1 macrophages can induce the differentiation of Th17 cells, which express high levels of RANKL, further promoting osteoclastogenesis and alveolar bone destruction.47 Our findings show that knockout of C3aR decreases the number of M1 macrophages and mitigates alveolar bone loss in mice with periodontitis. Here, TNFSF11 is linked to periodontitis.