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Nihon Yakurigaku Zasshi. 2001 Apr;117(4):293-7.

[Role of EP4 receptor in bone resorption induced by PGE].

[Article in Japanese]

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  • 1Department of Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432 Horinouchi, Hachioji, Tokyo 192-0392, Japan.


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.

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