Document Detail


Prostaglandin E(2) (PGE(2)) induces the c-fos and c-jun expressions via the EP(1) subtype of PGE receptor in mouse osteoblastic MC3T3-E1 cells.
MedLine Citation:
PMID:  10666498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study examined which subtype(s) of PGE receptors is involved in the induction of c-fos and c-jun by PGE(2) in MC3T3-E1 cells. We also investigated the possibility that the induction of these genes is involved in the growth and differentiation of this cell line. PGE(2) dose-dependently induced c-fos and c-jun mRNA expressions in MC3T3-E1 cells. Of the PGE analogs, 17-phenyl-omega-trinor PGE(2) (EP(1) agonist) and sulprostone (EP(1)/EP(3) agonist) were far more potent than butaprost (EP(2) agonist) and 11-deoxy PGE(1) (EP(2)/EP(4) agonist) in inducing c-fos and c-jun mRNA expressions. Since MC3T3-E1 cells do not express the EP(3) subtype, these results suggest that PGE(2) induces c-fos and c-jun mRNA expressions through the EP(1) subtype of its receptor. In order to study the functional relevance of these protooncogenes, we then studied the effect of inhibition of their synthesis by the use of antisense oligonucleotide. Alkaline phosphatase (ALP) suppression by 17-phenyl-omega-trinor PGE(2) was reversed by antisense oligonucleotide for either c-fos or c-jun. These results suggest that PGE(2), via the EP(1) subtype of the PGE receptor, negatively modulates the transition from proliferation to the matrix maturation stage through the induction of c-fos and c-jun. However, antisense oligonucleotide for c-fos or c-jun did not alter the prostaglandin G/H synthase-2 mRNA expression induced by EP(1). Thus, it is possible that c-fos and c-jun inductions do not account for all the EP(1)-mediated PGE(2) actions in MC3T3-E1 cells.
Authors:
M Suda; K Tanaka; Y Sakuma; A Yasoda; A Ozasa; J Fukata; I Tanaka; S Narumiya; K Nakao
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Calcified tissue international     Volume:  66     ISSN:  0171-967X     ISO Abbreviation:  Calcif. Tissue Int.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-02-29     Completed Date:  2000-02-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905481     Medline TA:  Calcif Tissue Int     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  217-23     Citation Subset:  IM    
Affiliation:
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54, Shogoin-kawaharacho, Sakyo, Kyoto, 606-8507, Japan.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / drug effects,  metabolism
Animals
Cell Line
Cyclooxygenase 2
Dinoprostone / analogs & derivatives,  pharmacology*
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Genes, fos / genetics*
Genes, jun / genetics*
Isoenzymes / genetics
Mice
Oligodeoxyribonucleotides, Antisense / pharmacology
Osteoblasts / cytology,  drug effects*,  metabolism
Prostaglandin-Endoperoxide Synthases / genetics
RNA, Messenger / drug effects,  genetics,  metabolism
Receptors, Prostaglandin E / physiology*
Chemical
Reg. No./Substance:
0/17-phenyltrinorprostaglandin E2; 0/Isoenzymes; 0/Oligodeoxyribonucleotides, Antisense; 0/RNA, Messenger; 0/Receptors, Prostaglandin E; 0/prostanoid receptor EP1; 363-24-6/Dinoprostone; 60325-46-4/sulprostone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 3.1.3.1/Alkaline Phosphatase

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