title: Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.
abstract: Previous epidemiologic studies have suggested that periodontal disease is closely related to obesity and glucose tolerance. As the level of adiponectin, an adipocyte-derived cytokine, in plasma had been reported to decrease in obese and type 2 diabetes patients, we explored the role of adiponectin in the etiology of periodontitis using the D clone of RAW264, a clone that exhibits highly efficient osteoclast formation, to determine whether adiponectin acts as a regulatory molecule in osteoclast formation stimulated by lipopolysaccharide of periodontopathic bacteria. We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. These observations strongly suggest that adiponectin may function as a negative regulator of lipopolysaccharide/RANKL-mediated osteoclast formation in periodontal disease.
authors.affiliation: Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, Fukuoka, Japan. nyama@dent.kyushu-u.ac.jp
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Kukita
authors.forename: Yin-Ji
authors.initials: YJ
authors.lastname: Li
authors.forename: Jose Guillermo
authors.initials: JG
authors.lastname: Martinez Argueta
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Saito
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Hanazawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamashita
mesh_terms: D000189:Actinobacillus Infections; D052242:Adiponectin / Q000494:pharmacology*; D016976:Aggregatibacter actinomycetemcomitans / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010518:Periodontitis / Q000209:etiology* / Q000382:microbiology; D053245:RANK Ligand / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D052242:Adiponectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053245:RANK Ligand; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II