The Role of Prostaglandin E Receptor Subtypes (EP1, EP2, EP3, and EP4) in Bone Resorption: An Analysis Using Specific Agonists for the Respective EPs
PGE2 functions as a potent stimulator of bone resorption. The action of PGE2 is thought to be mediated by some PGE receptor subtypes present in osteoblastic cells. In this study, we examined the involvement of PGE receptor subtypes, EP1, EP2, EP3, and EP4, in PGE2-induced bone resorption using speci...
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Published in | Endocrinology (Philadelphia) Vol. 141; no. 4; pp. 1554 - 1559 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Endocrine Society
01.04.2000
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Subjects | |
Online Access | Get full text |
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Summary: | PGE2 functions as a potent stimulator of bone resorption.
The action of PGE2 is thought to be mediated by some PGE
receptor subtypes present in osteoblastic cells. In this study, we
examined the involvement of PGE receptor subtypes, EP1, EP2, EP3, and
EP4, in PGE2-induced bone resorption using specific
agonists for the respective EPs. In mouse calvaria 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. RT-PCR showed that osteoblastic
cells isolated from newborn mouse calvaria expressed all of the EPs
messenger RNA (mRNA). Both EP2 agonist and EP4 agonist induced cAMP
production and the expression of osteoclast differentiation factor
(ODF) mRNA in osteoblastic cells. Simultaneous addition of EP2 and EP4
agonists cooperatively induced cAMP production and ODF mRNA expression.
In mouse bone marrow cultures, EP2 and EP4 agonists moderately induced
osteoclast formation, but the simultaneous addition of the two agonists
cooperatively induced it, similar to that by PGE2. In
calvaria culture from EP4 knockout mice, a marked reduction in bone
resorption to PGE2 was found. In EP4 knockout mice, EP4
agonist failed to induce bone resorption, but EP2 agonist slightly, but
significantly, induced bone resorption. These findings suggest that
PGE2 stimulates bone resorption by a mechanism involving
cAMP and ODF, which is mediated mainly by EP4 and partially by EP2. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.141.4.7405 |