title: Substance P stimulates release of RANKL via COX-2 expression in human dental pulp cells.
abstract: OBJECTIVE
  Our previous study found that substance P (SP), a sensory neuropeptide, was expressed in the dental pulp of rats during experimental tooth movement. We examined the effects of SP on the production of prostaglandin (PG) E2 and the receptor activator of nuclear factor- B ligand (RANKL) by human dental pulp fi broblast-like (HDPF) cells.
  
  
  METHODS
  SP was added to cultured HDPF cells at concentrations ranging from of 10(-4) to 10(-12) mol/L. PGE2 and soluble RANKL (sRANKL) levels were determined using enzyme-linked immunosorbent assay kits. Gene expression was confi rmed by RT-PCR analysis. Pit formation assays using dentin slices were carried out to examine the effect of SP on osteoclastogenesis.
  
  
  RESULTS
  The levels of PGE2 and sRANKL increased in the presence of SP, though the increases were greater in the experimental groups in both a time- and concentration-dependent manner, and the increase of RANKL was partially mediated by PGE2. The gene expression of cyclooxygenase (COX)-2 and RANKL was up-regulated, and conditioned medium samples obtained from HDPF cells treated with SP induced bone resorption.
  
  
  CONCLUSIONS
  SP stimulated the production of PGE2 and RANKL, and promoted bone resorption. Therefore, SP may be involved in pulpal inflammation and root resorption during orthodontic tooth movement.
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo City, Chiba, 271-8587, Japan. kojima@mascat.nihon-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Kasai
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009578:Nitrobenzenes / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D013449:Sulfonamides / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009578:Nitrobenzenes; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013449:Sulfonamides; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D013373:Substance P; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone