title: Mitogen-activated protein kinases mediate interleukin-1beta-induced receptor activator of nuclear factor-kappaB ligand expression in human periodontal ligament cells.
abstract: OBJECTIVE
  Interleukin-1beta-stimulated receptor activator of nuclear factor-kappaB ligand (RANKL) expression in human periodontal ligament cells is partially mediated by endogenous prostaglandin E2, whereas mitogen-activated protein kinases (MAPKs) are implicated in regulating various interleukin-1-responsive genes. We investigated herein the involvement of MAPKs in interleukin-1beta-stimulated RANKL expression in human periodontal ligament cells.
  
  
  METHODS
  Human periodontal ligament cells were pretreated separately with specific inhibitors of MAPKs, including extracellular signal-regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and subsequently treated with interleukin-1beta. Following each treatment, the phosphorylation of each MAPK, the expression of RANKL, and the production of prostaglandin E2 were determined. RANKL activity was evaluated using an assay to determine the survival of prefusion osteoclasts.
  
  
  RESULTS
  Interleukin-1beta induced RANKL expression at the mRNA and protein levels, as well as RANKL activity in human periodontal ligament cells. Interleukin-1beta also activated extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal kinase. Pretreatment with each MAPK inhibitor partially, but significantly, suppressed interleukin-1beta-induced RANKL expression and its activity, as well as prostaglandin E2 production.
  
  
  CONCLUSIONS
  In human periodontal ligament cells, three types of MAPK inhibitor may abrogate RANKL expression and activity induced by interleukin-1beta, directly or indirectly through partial suppression of prostaglandin E2 synthesis. In addition, extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal kinase signals may co-operatively mediate interleukin-1beta-stimulated RANKL expression and its activity in those cells.
authors.affiliation: Department of Periodontology, Showa University School of Dentistry, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Oikawa
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Okamatsu
authors.forename: T
authors.initials: T
authors.lastname: Shinki
authors.forename: R
authors.initials: R
authors.lastname: Kamijo
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Hasegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002417:Cattle; D015232:Dinoprostone / Q000032:analysis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010006:Osteoblasts / Q000201:enzymology; D010010:Osteoclasts / Q000201:enzymology; D010513:Periodontal Ligament / Q000166:cytology / Q000201:enzymology*; D053245:RANK Ligand / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D053583:Interleukin-1beta; D053245:RANK Ligand; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone