title: Simvastatin inhibits lipopolysaccharide-induced osteoclastogenesis and reduces alveolar bone loss in experimental periodontal disease.
abstract: OBJECTIVE
  Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and have anti-inflammatory effects independent of cholesterol lowering. Recent clinical studies have indicated that statin intake has a beneficial effect on periodontal disease. However, the underlying mechanisms have not been well understood. In the current study, we employed a rat model with lipopolysaccharide (LPS)-induced periodontal disease and determined the effect of simvastatin, a commonly prescribed statin, on osteoclastogenesis, gingival inflammation and alveolar bone loss.
  
  
  METHODS
  Sprague-Dawley rats were injected with Aggregatibacter actinomycetemcomitans LPS in periodontal tissue three times per week for 8 wk and part of the rats with LPS injection were also given simvastatin via gavage. After the treatments, the rat maxillae were scanned by microcomputed tomography and the images were analyzed to determine alveolar bone loss. To explore the underlying mechanisms, the effect of simvastatin on osteoclastogenesis and gingival expression of proinflammatory cytokines were also determined by tartrate-resistant acid phosphatase staining and real-time polymerase chain reaction assays, respectively.
  
  
  RESULTS
  Results showed that LPS treatment markedly increased bone loss, but administration of simvastatin significantly alleviated the bone loss. Results also showed that LPS treatment stimulated osteoclastogenesis and the expression of inflammatory cytokines, but simvastatin significantly modulates the stimulatory effect of LPS on osteoclastogenesis and cytokine expression.
  
  
  CONCLUSIONS
  This study demonstrated that simvastatin treatment inhibits LPS-induced osteoclastogenesis and gingival inflammation and reduces alveolar bone loss, indicating that the intake of simvastatin may hinder the progression of periodontal disease.
authors.affiliation: Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: M F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: C J
authors.initials: CJ
authors.lastname: Haycraft
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: K L
authors.initials: KL
authors.lastname: Kirkwood
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology*; D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D005881:Gingiva / Q000737:chemistry / Q000187:drug effects; D005891:Gingivitis / Q000517:prevention & control; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D008439:Maxillary Diseases / Q000517:prevention & control; D010010:Osteoclasts / Q000187:drug effects*; D010510:Periodontal Diseases / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D000071681:Tartrate-Resistant Acid Phosphatase; D051193:Toll-Like Receptors / Q000187:drug effects; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D007527:Isoenzymes; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D019821:Simvastatin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: alveolar bone; inflammation; lipopolysaccharide; periodontal disease; simvastatin