Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2

K Ono; T Akatsu; T Murakami; M Nishikawa; M Yamamoto; N Kugai; K Motoyoshi; N Nagata

doi:10.1677/joe.0.158r001

Important role of EP4, a subtype of prostaglandin (PG) E receptor, in osteoclast-like cell formation from mouse bone marrow cells induced by PGE2

J Endocrinol. 1998 Sep;158(3):R1-5. doi: 10.1677/joe.0.158r001.

Authors

K Ono¹, T Akatsu, T Murakami, M Nishikawa, M Yamamoto, N Kugai, K Motoyoshi, N Nagata

Affiliation

¹ Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.

PMID: 9846175
DOI: 10.1677/joe.0.158r001

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alprostadil / analogs & derivatives
Alprostadil / pharmacology
Animals
Anti-Arrhythmia Agents / pharmacology*
Anti-Ulcer Agents / pharmacology
Biphenyl Compounds / pharmacology*
Bone Marrow Cells
Cell Differentiation / drug effects
Cells, Cultured
Depression, Chemical
Dinoprostone / pharmacology*
Dose-Response Relationship, Drug
Male
Mice
Osteoclasts / drug effects*
Polymerase Chain Reaction
Prostaglandins E, Synthetic / pharmacology
RNA, Messenger / analysis
Receptors, Prostaglandin E / agonists
Receptors, Prostaglandin E / antagonists & inhibitors*
Receptors, Prostaglandin E / drug effects
Receptors, Prostaglandin E / genetics
Receptors, Prostaglandin E / physiology*
Receptors, Prostaglandin E, EP4 Subtype

Substances

Anti-Arrhythmia Agents
Anti-Ulcer Agents
Biphenyl Compounds
Prostaglandins E, Synthetic
Ptger4 protein, mouse
RNA, Messenger
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP4 Subtype
AH 23848
Alprostadil
butaprost
Dinoprostone
11-deoxyprostaglandin E1