title: Prostaglandin E(2) is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii.
abstract: BACKGROUND
  Periodontitis is an inflammatory disease that often leads to destruction of alveolar bone; a number of bacteria in subgingival plaque are associated with bone destruction in periodontitis. To understand the mechanism of how periodontopathogens induce osteoclastogenesis, we determined which mediators are involved in the osteoclastogenesis.
  
  
  METHODS
  We investigated effects of sonicates from three periodontopathic bacteria, Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii, on osteoclast formation in a co-culture system of mouse calvaria-derived osteoblasts and bone marrow cells. The osteoclast formation was determined by tartrate resistant acid phosphatase (TRAP) staining. The expression of the receptor activator of nuclear factor-kappa B ligand (RANKL), prostaglandin E(2) (PGE(2)) and osteoprotegerin (OPG) in mouse calvaria-derived osteoblasts was determined by immunoassay.
  
  
  RESULTS
  Each bacterial sonicate induced the osteoclast formation in the co-culture system. These bacterial sonicates increased the expression of RANKL and PGE(2), and decreased the expression of OPG in osteoblasts. The addition of OPG, an inhibitor of RANKL, in the co-culture completely suppressed the osteoclastogenesis that was stimulated by each bacterial sonicate. Indomethacin, which is an inhibitor of PGE(2) synthesis, reduced more than 88% of the osteoclast formation induced by each bacterial sonicate. Indomethacin inhibited more than 80% of RANKL expression in osteoblasts induced by T. denticola and T. socranskii, and 59% by P. gingivalis. Indomethacin completely recovered the depression of OPG expression in osteoblasts by T. denticola and T. socranskii to the level of the untreated osteoblasts. Indomethacin recovered the reduction of OPG expression by P. gingivalis to 67%.
  
  
  CONCLUSIONS
  These findings suggest that the osteoclastogenesis by P. gingivalis, T. denticola, and T. socranskii is mediated by a RANKL-dependent pathway and that PGE(2) is a main factor in the pathway by the enhancing of RANKL expression and the depression of osteoprotegerin, a RANKL inhibitor.
authors.affiliation: Department of Oromaxillofacial Infection and Immunity, College of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Choi
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Moon
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Cha
authors.forename: Kih-Wan
authors.initials: KW
authors.lastname: Kim
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin; D010518:Periodontitis / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012886:Skull / Q000166:cytology; D018709:Statistics, Nonparametric; D000071681:Tartrate-Resistant Acid Phosphatase; D014208:Treponema / Q000472:pathogenicity*; D048373:Treponema denticola / Q000472:pathogenicity
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D015232:Dinoprostone; D007213:Indomethacin