title: Fluvastatin Inhibits Osteoclast Differentiation and Porphyromonas gingivalis Lipopolysaccharide-Induced Alveolar Bone Erosion in Mice.
abstract: Statins have been widely used to treat hypercholesterolemia. In addition to inhibition of cholesterol synthesis, recent reports suggest a bone anabolic property of statins. However, little notice has been paid to the direct effect of statins on osteoclastogenesis and bone resorption.
  
  
  
  The effect of fluvastatin on osteoclast differentiation was determined using in vitro culture of mouse bone marrow macrophages (BMMs) in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL). The role of fluvastatin on bone erosion was examined in the Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS)-induced alveolar bone loss model in mice.
  
  
  
  Fluvastatin significantly inhibited both RANKL- and LPS-induced osteoclast differentiation in mouse BMMs. Fluvastatin also markedly reduced expression of osteoclast differentiation marker genes Acp5, Calcr, and Ctsk as well as fusion markers Atp6v0d2 and Dcstamp. These were accompanied by decreased expression of c-Fos and nuclear factor of activated T cells cytoplasmic 1 transcription factors. Fluvastatin reduced generation of reactive oxygen species upon the addition of RANKL and LPS, suggesting an antioxidant role. Finally, administration of fluvastatin in mice conspicuously reduced Pg LPS-induced osteoclastogenesis and alveolar bone erosion in vivo.
  
  
  
  Combined, these results suggest fluvastatin directly inhibited osteoclastogenesis and efficiently blocked bone erosion.
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Nitin Kumar
authors.initials: NK
authors.lastname: Pokhrel
authors.affiliation: Department of Periodontology, School of Dentistry, Kyungpook National University.
authors.forename: Yong-Gun
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.|Institute for Hard Tissue and Bone Regeneration, Kyungpook National University.
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D016966:Porphyromonas gingivalis / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology; D012313:RNA / Q000302:isolation & purification; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D000077340:Fluvastatin; D012313:RNA; D016173:Macrophage Colony-Stimulating Factor
keywords: Alveolar bone loss; cell differentiation; osteoclasts; statins