title: Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and TLR4.
abstract: Toll-like receptors (TLRs) play a key role in the innate immune responses to periodontal pathogens in periodontal disease. The present study was performed to determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using a Porphyromonas gingivalis-associated ligature-induced periodontitis model in mice. Wild-type (WT), Tlr2(-/-), and Tlr4(-/-) mice (8 to 10 weeks old) in the C57/BL6 background were used. Silk ligatures were applied to the maxillary second molars in the presence or absence of live P. gingivalis infection. Ligatures were removed from the second molars on day 14, and mice were kept for another 2 weeks before sacrifice for final analysis (day 28). On day 14, there were no differences in alveolar bone resorption and gingival RANKL expression between mice treated with ligation plus P. gingivalis infection and mice treated with ligation alone. Gingival interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) expression was increased, whereas IL-10 expression was decreased in WT and Tlr2(-/-) mice but not in Tlr4(-/-) mice. On day 28, WT and Tlr4(-/-) mice treated with ligation plus P. gingivalis infection showed significantly increased bone loss and gingival RANKL expression compared to those treated with ligation alone, whereas such an increase was diminished in Tlr2(-/-) mice. Gingival TNF-α upregulation and IL-10 downregulation were observed only in WT and Tlr4(-/-) mice, not in Tlr2(-/-) mice. In all mice, bone resorption induced by ligation plus P. gingivalis infection was antagonized by local anti-RANKL antibody administration. This study suggests that P. gingivalis exacerbates ligature-induced, RANKL-dependent periodontal bone resorption via differential regulation of TLR2 and TLR4 signaling.
authors.affiliation: The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, Massachusetts, USA The Fourth Hospital of Harbin Medical University, Department of Stomatology, Harbin, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: The Fourth Hospital of Harbin Medical University, Department of Stomatology, Harbin, China.
authors.forename: Liangjia
authors.initials: L
authors.lastname: Bi
authors.affiliation: The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, Massachusetts, USA Peking University School and Hospital of Stomatology, Department of Periodontology, Beijing, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yu
authors.affiliation: The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, Massachusetts, USA.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kawai
authors.affiliation: The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, Massachusetts, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Taubman
authors.affiliation: The Fourth Hospital of Harbin Medical University, Department of Radiology, Harbin, China shenbzh@vip.sina.com xhan@forsyth.org.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.affiliation: The Forsyth Institute, Department of Immunology and Infectious Diseases, Cambridge, Massachusetts, USA shenbzh@vip.sina.com xhan@forsyth.org.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Han
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D001862:Bone Resorption; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010518:Periodontitis / Q000382:microbiology* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D053245:RANK Ligand / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D053245:RANK Ligand; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C505689:Tnfsf11 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4