Based on the overall results of the present study, our working hypothesis is that, in the periodontitis environment, LPS released by the bacteria interacts with TLR4 on the recruited endogenous monocytes to promote the polarization of these cells toward pro‐inflammatory macrophages (M1) and stimulate M1 to secrete pro‐inflammatory cytokines such as TNF‐α, which then stimulates receptor activator of nuclear factor kappa‐B ligand (RANKL) expression on osteoblasts. The gene discussed is TNFSF11; the disease is periodontitis.