Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/79248
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dc.contributorDepartment of Applied Biology and Chemical Technology-
dc.contributorChinese Mainland Affairs Office-
dc.creatorHo, MX-
dc.creatorPoon, CCW-
dc.creatorWong, KC-
dc.creatorQiu, ZC-
dc.creatorWong, MS-
dc.date.accessioned2018-11-05T01:45:09Z-
dc.date.available2018-11-05T01:45:09Z-
dc.identifier.urihttp://hdl.handle.net/10397/79248-
dc.language.isoenen_US
dc.publisherFrontiers Research Foundationen_US
dc.rightsCopyright © 2018 Ho, Poon, Wong, Qiu and Wong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rightsThe following publication Ho, M. X., Poon, C. C. W., Wong, K. C., Qiu, Z. C., & Wong, M. S. (2018). Icariin, but not genistein, exerts osteogenic and anti-apoptotic effects in osteoblastic cells by selective activation of non-genomic ERα signaling. Frontiers in pharmacology, 9, 474, 1-17 is available at https://dx.doi.org/10.3389/fphar.2018.00474en_US
dc.subjectPhytoestrogensen_US
dc.subjectOsteoblastsen_US
dc.subjectApoptosisen_US
dc.subjectMAPK/ERKen_US
dc.subjectPI3K/Akten_US
dc.titleIcariin, but not genistein, exerts osteogenic and anti-apoptotic effects in osteoblastic cells by selective activation of non-genomic ER alpha signalingen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage1en_US
dc.identifier.epage17en_US
dc.identifier.volume9en_US
dc.identifier.doi10.3389/fphar.2018.00474en_US
dcterms.abstractGenistein and icariin are flavonoid compounds that exhibit estrogen-like properties in inducing bone formation and reducing bone loss associated with estrogen deficiency in both preclinical and clinical studies. However, the mechanisms that are involved in mediating their estrogenic actions in bone cells are far from clear. The present study aimed to study the signaling pathways that mediate the estrogenic actions of genistein and icariin in osteoblastic cells. The effects of genistein and icariin on the activation of estrogen receptor (ER) and the downstream mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in murine osteoblastic MC3T3-E1 cells and rat osteoblastic UMR-106 cells were studied. As expected, genistein displayed higher binding affinity toward ER beta than ER alpha and significantly induced estrogen response element (ERE)-dependent transcription in UMR-106 cells in a dose-dependent manner. In contrast, icariin failed to bind to ER alpha or ER beta and did not induce ERE-dependent transcription in UMR-106 cells at 10(-10) to 10(-7) M. The effects of genistein (10 nM) and icariin (0.1 mu M) on cell proliferation and differentiation in osteoblastic UMR-106 cells were abolished in the presence of ER antagonist ICI 182,780 (1 mu M), MAPK inhibitor U0126 (10 mu M), and PI3K inhibitor LY294002 (10 mu M). Genistein at 10 nM rapidly induced ERK1/2 phosphorylation at 5-10 min in UMR-106 cells and the phosphorylation of ER a at both Ser118 and Ser167 in both MC3T3-E1 and transfected UMR-106 cells whereas icariin at 0.1 mu M rapidly activated both ERK1/2 and Akt phosphorylation in UMR-106 cells and subsequent ER a phosphorylation at both Ser118 and Ser167 in MC3T3-E1 and transfected UMR-106 cells. Confocal imaging studies confirmed that the phosphorylation of ER a at Ser 118 and Ser 167 by genistein and icariin in MC3T3-E1 cells was mediated via MAPK-and PI3K-dependent pathway, respectively. Furthermore, our studies showed that icariin exerted stronger anti-apoptotic effects than genistein and 17 beta-estradiol (E2) and inhibited the cleavage of downstream caspase-3 in MC3T3-E1 cells induced by a potent PI3K inhibitor, PI828 (at 2 mu M). These results indicated that the mechanisms that mediate the estrogenic actions of icariin in osteoblastic cells are different from those of genistein.-
dcterms.accessRightsopen access-
dcterms.bibliographicCitationFrontiers in pharmacology, May 2018, v. 9, 474, p. 1-17-
dcterms.isPartOfFrontiers in pharmacology-
dcterms.issued2018-05-
dc.identifier.isiWOS:000431875400001-
dc.identifier.scopus2-s2.0-85047006745-
dc.identifier.pmid29867480-
dc.identifier.eissn1663-9812en_US
dc.identifier.artn474en_US
dc.identifier.rosgroupid2017004582-
dc.description.validate201810 bcrcen_US
dc.description.oaVersion of Record-
dc.identifier.FolderNumbera0691-n05-
dc.identifier.SubFormID947-
dc.description.fundingSourceRGC-
dc.description.fundingText15103614-
dc.description.pubStatusPublished-
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