AIM: To identify osteoclastogenic macrophage subsets and their regulatory mechanisms in periodontitis. METHODS: We integrated single-cell RNA sequencing datasets from human and murine periodontitis to construct a comprehensive macrophage and monocyte atlas. Employing functional enrichment, cell-cell communication, pseudotime, transcription factor, and machine learning analyses, we characterized and selected the specific macrophage subset involved in cell interactions. In vitro and in vivo experiments, including enzyme-linked immunosorbent assay, TRAP staining, micro-CT, qPCR, flow cytometry, and immunofluorescence staining, were performed to dissect the osteoclastogenic potential of specific macrophage subsets and to identify the key pathways. RESULTS: We discovered that the IL7R CONCLUSION: Our study identifies IL7R