title: Platelet-activating factor receptor blockade ameliorates Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice.
abstract: Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by oral biofilm-producing microorganisms, such as Aggregatibacter actinomycetemcomitans. The levels of the phospholipid platelet-activating factor (PAF) in the saliva, gingival crevicular fluid, and periodontal tissues are significantly increased during inflammatory conditions, such as PD, but the exact mechanism that links PAF to alveolar bone resorption is not well understood. In the current study, alveolar bone resorption was induced by experimental PD through the oral inoculation of A. actinomycetemcomitans in wild-type (WT) and PAF receptor knockout (Pafr(-/-)) mice. In vitro experiments using A. actinomycetemcomitans lipopolysaccharide (LPS)-stimulated RAW 264.7 cells treated with a PAF receptor antagonist (UK74505) were also performed. The expression of lyso-PAF acetyltransferase in periodontal tissues was significantly increased 3 h after A. actinomycetemcomitans LPS injection in mice. WT and Pafr(-/-) mice that were subjected to oral inoculation of A. actinomycetemcomitans presented neutrophil accumulation and increased levels of CXCL-1 and tumor necrosis factor alpha (TNF-α) in periodontal tissues. However, Pafr(-/-) mice presented less alveolar bone loss than WT mice. The in vitro blockade of the PAF receptor impaired the resorptive activity of A. actinomycetemcomitans LPS-activated osteoclasts. In conclusion, this study shows for the first time that the blockade of PAF receptor may contribute to the progression of PD triggered by A. actinomycetemcomitans by directly affecting the differentiation and activity of osteoclasts.
authors.affiliation: Department of Microbiology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mila Fernandes Moreira
authors.initials: MF
authors.lastname: Madeira
authors.forename: Celso Martins
authors.initials: CM
authors.lastname: Queiroz-Junior
authors.forename: Graciela Mitre
authors.initials: GM
authors.lastname: Costa
authors.forename: Silvia Maria Cordeiro
authors.initials: SM
authors.lastname: Werneck
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisalpino
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Tarcília Aparecida
authors.initials: TA
authors.lastname: Silva
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Souza
mesh_terms: D016301:Alveolar Bone Loss / Q000473:pathology; D000818:Animals; D001862:Bone Resorption; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology; D005881:Gingiva / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010010:Osteoclasts / Q000378:metabolism; D015661:Pasteurellaceae / Q000472:pathogenicity*; D016871:Pasteurellaceae Infections / Q000382:microbiology / Q000473:pathology*; D010510:Periodontal Diseases / Q000382:microbiology / Q000473:pathology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000172:deficiency; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000172:deficiency
chemical_list: D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor