Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2.
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.
Ono
K
K
Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Akatsu
T
T
Murakami
T
T
Nishikawa
M
M
Yamamoto
M
M
Kugai
N
N
Motoyoshi
K
K
Nagata
N
N
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
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