Porphyromonas gingivalis stimulates bone resorption by enhancing RANKL (Receptor Activator of NF-κB Ligand) through activation of toll-like receptor 2 in osteoblasts

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dc.contributor.authorKassem, Ali
dc.contributor.authorHenning, Petra
dc.contributor.authorLundberg, Pernilla
dc.contributor.authorSouza, Pedro Paulo Chaves de [UNESP]
dc.contributor.authorLindholm, Catharina
dc.contributor.authorLerner, Ulf H.
dc.contributor.institutionUmeå University
dc.contributor.institutionSahlgrenska Academy at University of Gothenburg
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-12-07T15:36:57Z
dc.date.available2015-12-07T15:36:57Z
dc.date.issued2015-08-14
dc.description.abstractPeriodontitis has been associated with rheumatoid arthritis. In experimental arthritis, concomitant periodontitis caused by oral infection with Porphyromonas gingivalis enhances articular bone loss. The aim of this study was to investigate how lipopolysaccharide (LPS) from P. gingivalis stimulates bone resorption. The effects by LPS P. gingivalis and four other TLR2 ligands on bone resorption, osteoclast formation, and gene expression in wild type and Tlr2-deficient mice were assessed in ex vivo cultures of mouse parietal bones and in an in vivo model in which TLR2 agonists were injected subcutaneously over the skull bones. LPS P. gingivalis stimulated mineral release and matrix degradation in the parietal bone organ cultures by increasing differentiation and formation of mature osteoclasts, a response dependent on increased RANKL (receptor activator of NF-κB ligand). LPS P. gingivalis stimulated RANKL in parietal osteoblasts dependent on the presence of TLR2 and through a MyD88 and NF-κB-mediated mechanism. Similarly, the TLR2 agonists HKLM, FSL1, Pam2, and Pam3 stimulated RANKL in osteoblasts and parietal bone resorption. LPS P. gingivalis and Pam2 robustly enhanced osteoclast formation in periosteal/endosteal cell cultures by increasing RANKL. LPS P. gingivalis and Pam2 also up-regulated RANKL and osteoclastic genes in vivo, resulting in an increased number of periosteal osteoclasts and immense bone loss in wild type mice but not in Tlr2-deficient mice. These data demonstrate that LPS P. gingivalis stimulates periosteal osteoclast formation and bone resorption by stimulating RANKL in osteoblasts via TLR2. This effect might be important for periodontal bone loss and for the enhanced bone loss seen in rheumatoid arthritis patients with concomitant periodontal disease.en
dc.description.affiliationUmeå University, Department of Molecular Periodontology
dc.description.affiliationSahlgrenska Academy at University of Gothenburg, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition at Institute for Medicine
dc.description.affiliationSahlgrenska Academy at University of Gothenburg, Department of Rheumatology and Inflammation Research, Institute for Medicine
dc.description.affiliationUnespUniversidade Estadual Paulista, Departamento de Fisiologia e Patologia, Faculdade de Odontologia de Araraquara
dc.format.extent20147-20158
dc.identifierhttp://dx.doi.org/10.1074/jbc.M115.655787
dc.identifier.citationThe Journal Of Biological Chemistry, v. 290, n. 33, p. 20147-20158, 2015.
dc.identifier.doi10.1074/jbc.M115.655787
dc.identifier.issn1083-351X
dc.identifier.pmcPMC4536425
dc.identifier.pubmed26085099
dc.identifier.urihttp://hdl.handle.net/11449/131523
dc.language.isoeng
dc.publisherThe American Society for Biochemistry and Molecular Biology
dc.relation.ispartofThe Journal Of Biological Chemistry
dc.rights.accessRightsAcesso restrito
dc.sourcePubMed
dc.subjectBoneen
dc.subjectInflammationen
dc.subjectInnate immunityen
dc.subjectOsteoblasten
dc.subjectOsteoclasten
dc.subjectToll-like receptor (TLR)en
dc.titlePorphyromonas gingivalis stimulates bone resorption by enhancing RANKL (Receptor Activator of NF-κB Ligand) through activation of toll-like receptor 2 in osteoblastsen
dc.typeArtigo
dcterms.rightsHolder© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.© 2015 By The American Society For Biochemistry And Molecular Biology, Inc.
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araraquarapt

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