Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

Int J Oral Sci. 2015 Dec 18;7(4):242-9. doi: 10.1038/ijos.2015.28.


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 (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF 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, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor κB 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 NaF. Taken together, our data demonstrate that NaF 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 NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / drug effects
  • Alveolar Bone Loss / microbiology
  • Alveolar Bone Loss / prevention & control*
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Bacteroidaceae Infections / microbiology
  • Bacteroidaceae Infections / prevention & control
  • Bone Density Conservation Agents / therapeutic use*
  • Cathepsin K / drug effects
  • Interleukin-1beta / drug effects
  • Interleukin-6 / analysis
  • Interleukin-8 / drug effects
  • Isoenzymes / drug effects
  • Macrophage Colony-Stimulating Factor / drug effects
  • Male
  • Matrix Metalloproteinase 9 / drug effects
  • Osteoclasts / drug effects*
  • Periodontitis / microbiology
  • Periodontitis / prevention & control
  • Porphyromonas gingivalis / drug effects*
  • RANK Ligand / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Fluoride / therapeutic use*
  • Tartrate-Resistant Acid Phosphatase
  • Transcription Factors / drug effects
  • X-Ray Microtomography / methods


  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Bone Density Conservation Agents
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Isoenzymes
  • NFATC1 protein, rat
  • RANK Ligand
  • Transcription Factors
  • Macrophage Colony-Stimulating Factor
  • Sodium Fluoride
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K
  • Ctsk protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat