[Role of EP4 receptor in bone resorption induced by PGE].
Prostaglandin E2 (PGE2) acts as a potent stimulator of bone resorption. We examined PGE2-induced bone resorption using mice lacking each subtype (EP1, EP2, EP3 and EP4) of PGE receptor and identified the PGE receptor subtype(s) mediating PGE2 action. In calvarial culture from EP1-, EP2-, and EP3- knockout mice, PGE2 stimulated bone resorption to a similar extent to that found in calvaria from the wild-type mice. On the other hand, a marked reduction in bone resorption in response to PGE2 was found in the calvarial culture from EP4-knockout/mice. DbcAMP greatly stimulated bone resorption similarly in both wild-type and EP4-knockout mice. In mouse calvarial cultures, EP4-agonist markedly stimulated bone resorption, but its maximal stimulation was less than that induced by PGE2. EP2-agonist also stimulated bone resorption, but only slightly, EP1- and EP3-agonists did not stimulate it at all. These findings suggest that PGE2 stimulates bone resorption by a mechanism involving cAMP, which is mediated mainly by EP4 and partially by EP2.
Miyaura
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Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432 Horinouchi, Hachioji, Tokyo 192-0392, Japan. chisato@ps.toyaku.ac.jp
D000818:Animals; D001862:Bone Resorption; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000502:physiology; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology; D011458:Prostaglandins E / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype
D011458:Prostaglandins E; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP