title: Endoplasmic reticulum stress response and bone loss in experimental periodontitis in mice.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress is the cell response that activates the unfolded protein response (UPR) pathway in a variety of conditions, such as inflammation and bone metabolism. The UPR may be associated with the pathogenesis of periodontal disease because the disease is inflammatory in nature, and alveolar bone resorption is a characteristic feature of the disease. However, the relationship between ER stress and alveolar bone resorption observed in periodontal disease remains elusive.
  
  
  METHODS
  C57BL/6 mice were orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, in the presence or absence of a chemical chaperone, 4-phenylbutyrate (4-PBA). The gene expression of UPR-related molecules and cytokines in gingival tissues were analyzed using real-time polymerase chain reaction, and alveolar bone resorption and osteoclast numbers were evaluated histologically. The in vitro effect of 4-PBA on the differentiation of mouse bone marrow cells induced by receptor activator of nuclear factor-κB ligand in the presence of macrophage colony-stimulating factor was analyzed.
  
  
  RESULTS
  The gene expression levels of UPR-related molecules and proinflammatory cytokines and alveolar bone resorption were significantly increased in P. gingivalis-administered mice. UPR-related gene expression and alveolar bone resorption were significantly suppressed by the administration of 4-PBA. However, no effect of 4-PBA was observed for proinflammatory cytokine expression in gingival tissues. Osteoclastic differentiation of bone marrow cells was also suppressed by 4-PBA with a concomitant reduction in the gene expression of cathepsin K and tartrate-resistant alkaline phosphatase genes.
  
  
  CONCLUSIONS
  ER stress induced by oral administration of P. gingivalis is involved in alveolar bone resorption independent of inflammatory cytokines in mice.
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Dental Educational Research Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Domon
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D056657:Cathepsin K / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005881:Gingiva / Q000737:chemistry / Q000187:drug effects; D018836:Inflammation Mediators / Q000032:analysis; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018832:Molecular Chaperones / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010518:Periodontitis / Q000382:microbiology*; D010654:Phenylbutyrates / Q000494:pharmacology; D016966:Porphyromonas gingivalis / Q000502:physiology; D053245:RANK Ligand / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase / Q000187:drug effects; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D018832:Molecular Chaperones; D010654:Phenylbutyrates; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C075773:4-phenylbutyric acid; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: Porphyromonas gingivalis; endoplasmic reticulum stress; osteoclast; periodontitis