Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors.Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases.Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride(Na F) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. Na F strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin(IL)-1β, matrix metalloproteinase 9(MMP9), and tartrate-resistant acid phosphatase,which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect,Na F inhibited osteoclast formation caused by the differentiation factor RANKL(receptor activator of nuclear factor kB ligand)and macrophage colony-stimulating factor(M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells(NFAT) c1 was also abrogated by Na F. Taken together, our data demonstrate that Na F inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9.The in vivo effect of Na F on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of Na F for treating periodontal diseases. Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte / macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (Na F) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. Na F strongly inhibited the P. gingivalis-induced alveolar bone loss. was accompanied by decreased levels of cathepsin K, interleukin (IL) -1β, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti- Osteoclastogenic effect, Na F blocked osteoclast formation caused by the differentiation factor RANKL (receptor a ctivator of nuclear factor kB ligand and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by Na F. Taken together, our data demonstrate that Na F inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc 1, ultimately leading to the suppressed expression of cathepsin K and MMP 9. The in vivo effect of Na F on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of Na F for treating periodontal diseases.