title: Regulation of Nur77 gene expression by prostanoids in cementoblastic cells.
abstract: OBJECTIVE
  The inflammatory cytokine interleukin-1 (IL-1) decreases mineralisation by immortalized mouse-derived cementoblastic cells (OC-CM cells), whilst various prostanoids, including fluprostenol (flup) increase it. Subtraction hybridisation conducted on flup minus IL-1-treated OC-CM cells revealed that one of the primary response genes preferentially induced by flup is the transcription factor Nur77. The objective of this study was to examine the signal transduction cascades regulating prostanoid induction of Nur77 gene expression in OC-CM cells.
  
  
  METHODS
  Confluent OC-CM cells were treated with prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), specific activators of the various EP prostanoid receptors and of the FP prostanoid receptor, and direct activators/inhibitors of the cyclic AMP-protein kinase A (PKA), protein kinase C (PKC) and intracellular calcium pathways. Nur77 gene expression was examined by mRNA extraction and Northern blot analysis.
  
  
  RESULTS
  PGE(2) and PGF(2alpha) treatment of OC-CM cells significantly increased Nur77 mRNA expression in a time- and dose-dependent fashion. Both the EP1 prostanoid receptor-specific activator 16,16-dimethyl-PGE(2) and the FP prostanoid receptor-specific activator flup significantly increased Nur77 gene expression by OC-CM cells as compared to vehicle-treated controls. Increase in Nur77 gene expression was also observed when direct activators of the PKA, PKC and intracellular calcium pathways were used to treat OC-CM cells. Direct inhibition of the PKA, PKC and intracellular calcium pathways abrogated Nur77 gene expression induced by OC-CM cell treatment with PGE(2) and PGF(2alpha).
  
  
  CONCLUSIONS
  Nur77 is a primary gene expressed by OC-CM cells and its induction appears to be mediated by the PKA, PKC and intracellular calcium pathways. Nur77 may affect expression of downstream target genes in OC-CM cells and partially regulate cementoblast cell function.
authors.affiliation: Division of Associated Clinical Specialties, Section of Periodontics, School of Dentistry, University of California, Los Angeles, CA 90095, United States.
authors.forename: Sanda M
authors.initials: SM
authors.lastname: Moldovan
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Nervina
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tetradis
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Camargo
mesh_terms: D000527:Alprostadil / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects; D003739:Dental Cementum / Q000378:metabolism*; D015237:Dinoprost / Q000819:agonists / Q000494:pharmacology; D015232:Dinoprostone / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D016595:Misoprostol / Q000819:agonists / Q000494:pharmacology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics*; D011453:Prostaglandins / Q000235:genetics* / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000819:agonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors
chemical_list: C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C034671:prostaglandin F2alpha receptor; D016595:Misoprostol; D005576:Colforsin; C006326:fluprostenol; C016767:sulprostone; D015237:Dinoprost; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone