Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.
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.
Yamaguchi
Noboru
N
Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, Fukuoka, Japan. nyama@dent.kyushu-u.ac.jp
Kukita
Toshio
T
Li
Yin-Ji
YJ
Martinez Argueta
Jose Guillermo
JG
Saito
Toshiyuki
T
Hanazawa
Shigemasa
S
Yamashita
Yoshihisa
Y
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
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