title: PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo.
abstract: OBJECTIVE
  In this study, we aimed to clarify the precise mechanism underlying lipopolysaccharide (LPS)-induced osteoclastogenesis in periodontal disease with a special reference to double-stranded RNA-dependent protein kinase (PKR).
  
  
  METHODS
  We dissected the role of PKR in LPS-induced osteoclast differentiation and function using primary mouse bone marrow cells and RAW264.7 pre-osteoclastic cell line. We used a rat experimental periodontitis (PD) model induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD rat) and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss in PD rats.
  
  
  RESULTS
  Protein kinase is strongly upregulated and phosphorylated by LPS in the osteoclasts. The inhibition of PKR suppressed LPS-stimulated osteoclast formation and activation. PKR inhibition also suppressed the LPS-mediated activation of NF-κB and MAPK, which are critical pathways for osteoclastogenesis. High expressions of PKR were detected in osteoclasts of PD rats, and the treatment with C16 effectively prevented alveolar bone destruction in PD rats.
  
  
  CONCLUSIONS
  PKR plays a pivotal role in LPS-induced bone loss in PD and, thus, has potential as a therapeutic target for PD.
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Teramachi
authors.affiliation: Department of Periodontology and Endodontology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.|Department of Periodontology and Endodontology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Basic Science, School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Baba
authors.affiliation: Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Morimoto
authors.affiliation: Department of Periodontology and Endodontology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Haneji
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control; D000818:Animals; D002460:Cell Line; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C000617853:GW 506033X; D007211:Indoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013844:Thiazoles; D019892:eIF-2 Kinase
keywords: double-stranded RNA-dependent protein kinase; lipopolysaccharide; osteoclastogenesis; periodontal disease