title: Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis.
abstract: OBJECTIVE
  The purpose of this study was to assess the role of anti-bone resorptive agents and an anti-inflammatory compound in murine Porphyromonas gingivalis (P. gingivalis)-induced periodontitis.
  
  
  METHODS
  Six randomly assigned groups were administered vehicle (saline, control) (n = 6), P. gingivalis infection only (untreated) (n = 6), human-Fc (n = 4), Kavain (n = 6), OPG-Fc (n = 6) and Receptor activator of nuclear factor-kappa B (RANK)-Fc (n = 6) intraperitoneally at day 0, 3 and 7. Animals were euthanized on day 10 and subjected to comprehensive histomorphometric analysis. To capture the progress of inflammation, serum samples were collected at days 0, 3, 7 and 10 for levels of pro-inflammatory cytokines.
  
  
  RESULTS
  Compared with control group, OPG-Fc, RANK-Fc and Kavain treatment showed significant bone loss reduction with OPG-Fc performing better than RANK-Fc or Kavain. Epithelial down-growth showed significant reduction in treatment groups with OPG-Fc performing better than RANK-Fc or Kavain. Finally, Kavain, OPG-Fc and RANK-Fc-treated mice displayed reduced inflammatory cell counts and cytokine expression particularly at day 7 postinfection.
  
  
  CONCLUSIONS
  RANKL antagonists and Kavain effectively reduced alveolar bone loss in P. gingivalis-induced periodontitis in our mice model. Compared with RANK-Fc, Kavain-treated animals showed milder improvement of bone and connective tissue inflammation. Therapeutic implications in the prevention of periodontal bone loss are discussed.
authors.affiliation: Center for Anti-Inflammatory Therapeutics, School of Dental Medicine, Boston University, Boston, MA 02118-2518, USA.
authors.forename: Huaiping
authors.initials: H
authors.lastname: Yuan
authors.forename: Rohit
authors.initials: R
authors.lastname: Gupte
authors.forename: Sami
authors.initials: S
authors.lastname: Zelkha
authors.forename: Salomon
authors.initials: S
authors.lastname: Amar
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053244:Osteoprotegerin / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism*; D016966:Porphyromonas gingivalis; D011753:Pyrones / Q000494:pharmacology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D053244:Osteoprotegerin; D011753:Pyrones; D053245:RANK Ligand; C517736:Rank-Fc; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C011889:kavain