title: Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Oral Health, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.affiliation: Department of Dental Hygiene, Howon University, Gunsan, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Preventive and Public Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Kazumune
authors.initials: K
authors.lastname: Arikawa
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Shimosaka
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Infection Control, Division of Microbiology, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Toshizo
authors.initials: T
authors.lastname: Toyama
authors.affiliation: Department of Infection Control, Division of Microbiology, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Radiopraxis Science, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kawamata
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Preventive and Public Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Taguchi
authors.affiliation: Department of Infection Control, Division of Microbiology, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Nobushiro
authors.initials: N
authors.lastname: Hamada
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Preventive and Public Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nasu
authors.affiliation: Department of Oral Health, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Research Institute of Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.|Department of Preventive and Public Oral Health, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Shibutani
mesh_terms: D000135:Acid Phosphatase / Q000187:drug effects; D016301:Alveolar Bone Loss / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016866:Bacteroidaceae Infections / Q000382:microbiology / Q000517:prevention & control; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D056657:Cathepsin K / Q000187:drug effects; D053583:Interleukin-1beta / Q000187:drug effects; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D010518:Periodontitis / Q000382:microbiology / Q000517:prevention & control; D016966:Porphyromonas gingivalis / Q000187:drug effects*; D053245:RANK Ligand / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000627:therapeutic use*; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000187:drug effects; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; C584440:NFATC1 protein, rat; D053245:RANK Ligand; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor; D012969:Sodium Fluoride; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534133:Ctsk protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat