title: 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.
abstract: 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.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54, Shogoin-kawaharacho, Sakyo, Kyoto, 606-8507, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suda
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuma
authors.forename: A
authors.initials: A
authors.lastname: Yasoda
authors.forename: A
authors.initials: A
authors.lastname: Ozasa
authors.forename: J
authors.initials: J
authors.lastname: Fukata
authors.forename: I
authors.initials: I
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
authors.forename: K
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype
chemical_list: C092396:17-phenyltrinorprostaglandin E2; D007527:Isoenzymes; D020319:Oligodeoxyribonucleotides, Antisense; C545636:Ptger1 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; C016767:sulprostone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000469:Alkaline Phosphatase; D015232:Dinoprostone