title: Prostanoids induce egr1 gene expression in cementoblastic OCCM cells.
abstract: OBJECTIVE
  Prostanoids that activate protein kinase C signaling are potent anabolic stimulators of cementoblastic OCCM cells. Using cDNA subtractive hybridization, we identified early growth response gene-1 (egr1) as a prostanoid-induced gene. Egr1, a zinc-finger transcription factor expressed during tooth development, regulates cell growth and differentiation. We hypothesize that Egr1 may mediate part of the prostanoid-induced anabolic effect in cementoblasts. Our objective was to characterize prostanoid-induced egr1 gene expression in OCCM cells.
  
  
  METHODS
  Total RNA and proteins were assayed by northern blot and western immunoblot assays.
  
  
  RESULTS
  Prostaglandin E2-, prostaglandin F2alpha- and fluprostenol-induced egr1 mRNA levels peaked at 0.5 h and returned to baseline by 4 h. Prostaglandin F2alpha and fluprostenol more potently induced egr1 compared with prostaglandin E2. The phorbol ester, phorbol 12-myristate 13-acetate, which activates protein kinase C signaling, induced egr1 mRNA levels 66-fold over the control, whereas forskolin (a cAMP-protein kinase A activator) and ionomycin (a calcium activator) had no effect. Protein kinase C inhibition significantly inhibited prostaglandin E2-, prostaglandin F2alpha- and fluprostenol-induced egr1 mRNA levels. Finally, prostanoids maximally induced Egr1 protein at 1 h.
  
  
  CONCLUSIONS
  egr1 is a primary response gene induced by prostaglandin E2, prostaglandin F2alpha and fluprostenol in OCCM cells through protein kinase C signaling, suggesting that Egr1 may be a key mediator of anabolic responses in cementoblasts. Cementum is vital for periodontal organ maintenance and regeneration. Periodontal ligament fibers (Sharpey's fibers) insert into bone and cementum, thereby supporting the tooth in the alveolus (1). If the periodontal organ is lost, its regeneration requires cementoblast differentiation in order to form new cementum for periodontal ligament fiber insertion. Early attempts to regenerate cementum have proven difficult and rarely generate sufficient tissue (2). A better understanding of the molecular and cellular regulators that promote cementoblast differentiation is critical for developing targeted periodontal regeneration.
authors.affiliation: Section of Oral Biology, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, CA 90095-1668, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pham
authors.forename: O
authors.initials: O
authors.lastname: Bezouglaia
authors.forename: P M
authors.initials: PM
authors.lastname: Camargo
authors.forename: J M
authors.initials: JM
authors.lastname: Nervina
authors.forename: S
authors.initials: S
authors.lastname: Tetradis
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003739:Dental Cementum / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D051766:Early Growth Response Protein 1 / Q000187:drug effects* / Q000235:genetics; D020536:Enzyme Activators / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D011453:Prostaglandins / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D016335:Zinc Fingers / Q000187:drug effects* / Q000235:genetics
chemical_list: D002273:Carcinogens; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D020536:Enzyme Activators; D007476:Ionophores; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D005576:Colforsin; C006326:fluprostenol; D015759:Ionomycin; D015237:Dinoprost; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate