title: Tannerella forsythia GroEL induces inflammatory bone resorption and synergizes with interleukin-17.
abstract: Tannerella forsythia is a major periodontal pathogen, and T. forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E2(PGE2) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. forsythia GroEL and IL-17 synergistically increased PGE2production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. forsythia GroEL injection, and simultaneous injection of T. forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Y-J
authors.identifier: 0000-0002-9785-0348
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: S-J
authors.initials: SJ
authors.lastname: An
authors.affiliation: Division of High-Risk Pathogen Research, Center for Infectious Diseases, Korea National Institute of Health, Cheongju-si, Chungcheongbuk-do, Korea.
authors.forename: H-R
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: H-K
authors.initials: HK
authors.lastname: Jun
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Korea.|Dental Research Institute, Seoul National University, Seoul, Korea.
authors.forename: B-K
authors.initials: BK
authors.lastname: Choi
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D018834:Chaperonin 60 / Q000378:metabolism* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000382:microbiology; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D007249:Inflammation; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D051379:Mice; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000276:immunology; D012886:Skull / Q000276:immunology / Q000473:pathology; D000070436:Tannerella forsythia / Q000276:immunology* / Q000472:pathogenicity*; D037521:Virulence Factors; D055114:X-Ray Microtomography
chemical_list: D018834:Chaperonin 60; D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D053244:Osteoprotegerin; D037521:Virulence Factors; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: bacterial chaperonin 60; calvarial bone resorption; interleukin-6; interleukin-8; osteoprotegerin; prostaglandin E2