title: GM-CSF and uPA are required for Porphyromonas gingivalis-induced alveolar bone loss in a mouse periodontitis model.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and urokinase-type plasminogen activator (uPA) can contribute to the progression of chronic inflammatory diseases with possible involvement of macrophages. In this study, we investigated the role of both GM-CSF and uPA in Porphyromonas gingivalis-induced experimental periodontitis using GM-CSF-/- and uPA-/- mice. Intra-oral inoculation of wild-type (WT) C57BL/6 mice with P. gingivalis resulted in establishment of the pathogen in plaque and a significant increase in alveolar bone resorption. The infected mice also exhibited a CD11b(+) CD86(+) macrophage infiltrate into the gingival tissue, as well as P. gingivalis-specific pro-inflammatory cytokine and predominantly IgG2b antibody responses. In comparison, intra-oral inoculation of P. gingivalis did not induce bone resorption and there was significantly less P. gingivalis recovered from plaque in GM-CSF-/- and uPA-/- mice. Furthermore, P. gingivalis did not induce a macrophage gingival infiltrate or activate isolated peritoneal macrophages from the gene-deficient mice. Pro-inflammatory P. gingivalis-specific T-cell cytokine responses and serum interferon-gamma (IFN-γ) and IgG2b concentrations were significantly lower in GM-CSF-/- mice. In uPA-/- mice, T-cell responses were lower but serum IFN-γ and IgG2b levels were comparable with WT mice levels. These results suggest that GM-CSF and uPA are both involved in the progression of experimental periodontitis, possibly via a macrophage-dependent mechanism(s).
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Roselind S
authors.initials: RS
authors.lastname: Lam
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Neil M
authors.initials: NM
authors.lastname: O'Brien-Simpson
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Lenzo
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Holden
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Gail C
authors.initials: GC
authors.lastname: Brammar
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Orth
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Walsh
authors.affiliation: Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fleetwood
authors.affiliation: Oral Health Cooperative Research Centre, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Reynolds
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003773:Dental Plaque / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D016130:Immunophenotyping; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010518:Periodontitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000502:physiology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014568:Urokinase-Type Plasminogen Activator