title: Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2.
abstract: Of various PGs, PGE1 and PGE2 are shown to be the most potent stimulators of osteoclastogenesis in vitro. PGE receptors have been classified into four subtypes, EP1-EP4. Little is known about PGE receptors functioning in bone cells. In this study, using mouse marrow culture, we investigated which PGE receptors are important in osteoclast-like cell (OCL) formation induced by PGE. 11-deoxy-PGE1 (EP2, EP3 and EP4 agonist) stimulated OCL formation potently. Butaprost (EP2 agonist) stimulated it slightly, while sulprostone (EP1 and EP3 agonist) and ONO-AP-324-01 (EP3 agonist) did not. AH23848B (EP4 antagonist) inhibited PGE2-induced OCL formation in a dose-dependent manner. The expression of EP4 mRNA in mouse bone marrow was confirmed by RT-PCR. The results indicate an important role of EP4 in PGE2-induced OCL formation in marrow cultures and suggest therapeutic potential of EP4 antagonists in some clinical conditions with accelerated bone resorption.
authors.affiliation: Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Akatsu
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Kugai
authors.forename: K
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: N
authors.initials: N
authors.lastname: Nagata
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype
chemical_list: D000889:Anti-Arrhythmia Agents; D000897:Anti-Ulcer Agents; D001713:Biphenyl Compounds; D011459:Prostaglandins E, Synthetic; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C046926:AH 23848; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone; C034008:11-deoxyprostaglandin E1