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dc.contributor.authorRen, Jian
dc.contributor.authorWu, Junhua
dc.date.accessioned2015-08-03T09:45:22Z
dc.date.available2015-08-03T09:45:22Z
dc.date.issued2012-03-06
dc.identifier.issn0171967X
dc.identifier.pmid22392527
dc.identifier.doi10.1007/s00223-012-9581-x
dc.identifier.urihttp://hdl.handle.net/10754/562124
dc.description.abstractEstrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.
dc.description.sponsorshipWe are indebted to Dr. Lynda Bonewald for her kind gift of MLO Y4 cells and thank Ms. Jennifer Rosser for help in arranging the transportation and logistics. This work was supported by the Nature Science Foundation of Shanghai, China (Grant 11ZR1440700).
dc.publisherSpringer Nature
dc.subjectCalcium ion
dc.subjectEstrogen
dc.subjectEstrogen receptor
dc.subjectGPR30
dc.subjectMAPK
dc.subjectOsteocyte
dc.title17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells
dc.typeArticle
dc.contributor.departmentImaging and Characterization Core Lab
dc.contributor.departmentAdvanced Nanofabrication, Imaging and Characterization Core Lab
dc.contributor.departmentCore Labs
dc.identifier.journalCalcified Tissue International
dc.contributor.institutionSchool of Stomatology, Tongji University, No. 399, Yanchang Middle Road, Shanghai 200072, China
kaust.personRen, Jian
dc.date.published-online2012-03-06
dc.date.published-print2012-05


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