IMPORTANT ROLE OF EP4, A SUBTYPE OF PROSTAGLANDIN (PG)-E RECEPTOR, INOSTEOCLAST-LIKE CELL-FORMATION FROM MOUSE BONE-MARROW CELLS INDUCED BY PGE(2)

Of various PGs, PGE(1) and PGE(2) are shown to be the most potent stim ulators of osteoclastogenesis in vitro. PGE receptors have been classi fied 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 c ell (OCL) formation induced by PGE. 11-deoxy-PGE(1) (EP2, EP3 and EP4 agonist) stimulated OCL formation potently. Butaprost (EP2 agonist) st imulated it slightly, while sulprostone (EP1 and EP3 agonist) and ONO- AP-324-01 (EP3 agonist) did not. AH23848B (EP4 antagonist) inhibited P GE(2)-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 PGE(2) induced OCL formation in marrow cultures and suggest therapeutic potential of EP4 antagonists i n some clinical conditions with accelerated bone resorption.