title: Prostaglandin E2 affects osteoblast biology in a dose-dependent manner: an in vitro study.
abstract: OBJECTIVE
  This study aimed to determine in vitro how exogenous PGE(2) affects the expression of genes in cultured osteoblasts by relative quantitation PCR.
  
  
  METHODS
  Cultured osteoblasts were exposed to 10(-3)M, 10(-5)M or 10(-7)M PGE(2) over 5, 10, 15 and 20 days.
  
  
  RESULTS
  RANKL expression was higher after 5 days of exposure (p<0.05), but thereafter reduced in those treated with the two lower doses of PGE(2) (p<0.01). RANKL/OPG ratio reported in favour of OPG gene expression and alkaline phosphatase gene expression increased in osteoblasts exposed to the two lower doses of the eicosanoid after 15 days. Conversely, prostaglandin E synthase, a cytokine produced during PGE(2) synthesis, gene expression was significantly reduced at 15 and 20 days (p<0.01 and 0.05 respectively). The results from this study add to the current knowledge of the mechanisms by which PGE(2) modulates the osteoblast biology in a dose-dependent manner.
  
  
  CONCLUSIONS
  It is proposed that PGE(2)at a low dose switch osteoblast's biology in favour of bone apposition by: first, inducing a significantly higher OPG gene expression overwhelming RANKL gene expression; second, reducing PGEs synthesis; and third, increasing ALP gene expression. An opposite effect is expected when the concentration of the eicosanoid overpass certain levels.
authors.affiliation: Faculty of Dentistry, University of Manitoba, D209-780 Bannatyne Ave, Winnipeg, MB, Canada. ramirezy@cc.umanitoba.ca
authors.forename: G O
authors.initials: GO
authors.lastname: Ramirez-Yanez
authors.forename: A L
authors.initials: AL
authors.lastname: Symons
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D000818:Animals; D018929:Cell Culture Techniques; D048430:Cell Shape; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000187:drug effects; D008297:Male; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000187:drug effects; D000071876:Prostaglandin-E Synthases; D053245:RANK Ligand / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D000469:Alkaline Phosphatase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone