Show simple item record

dc.contributor.authorGeoghegan, Ivor P.
dc.contributor.authorHoey, David A.
dc.contributor.authorMcNamara, Laoise M.
dc.date.accessioned2020-01-14T09:15:24Z
dc.date.available2020-01-14T09:15:24Z
dc.date.issued2019-03-15
dc.identifier.citationGeoghegan, Ivor P., Hoey, David A., & McNamara, Laoise M. (2019). Estrogen deficiency impairs integrin αvβ3-mediated mechanosensation by osteocytes and alters osteoclastogenic paracrine signalling. Scientific Reports, 9(1), 4654. doi: 10.1038/s41598-019-41095-3en_IE
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10379/15703
dc.description.abstractThe integrin alpha(v)beta(3) has been shown to play an important role in osteocyte mechanotransduction. It has been reported that there are fewer beta(3) integrin-containing cells in osteoporotic bone cells. Osteocytes cultured in vitro under estrogen deficient conditions demonstrate altered mechanotransduction. However, it is unknown whether the altered mechanotransduction in estrogen deficient osteocytes is directly associated with defective alpha(v)beta(3) expression or signalling. The objective of this study is to investigate the role of estrogen deficiency for regulating MLO-Y4 cell morphology, alpha(v)beta(3) expression, focal adhesion formation and mechanotransduction by osteocytes. Here, we report that estrogen withdrawal leads to a smaller focal adhesion area and reduced alpha(v)beta(3) localisation at focal adhesion sites, resulting in an increased Rankl/Opg ratio and defective Cox-2 responses to oscillatory fluid flow. Interestingly, alpha(v)beta(3) antagonism had a similar effect on focal adhesion assembly, Rankl/Opg ratio, and Cox-2 responses to oscillatory fluid flow. Taken together, our results provide the first evidence for a relationship between estrogen withdrawal and defective alpha(v)beta(3)-mediated signalling. Specifically, this study implicates estrogen withdrawal as a putative mechanism responsible for altered alpha(v)beta(3) expression and resultant changes in downstream signalling in osteocytes during post-menopausal osteoporosis, which might provide an important, but previously unidentified, contribution to the bone loss cascade.en_IE
dc.description.sponsorshipThis publication has emanated from research conducted with the financial support of Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under Grant Number 13/RC/2073 and Grant Number 14/IA/2884. The authors acknowledge funding from European Research Council (ERC) Starting Grant (336882) and Science Foundation Ireland (SFI) Grants 13/ERC/L2864 and 12/RC/2278. The MLO-Y4 cell line used in this study was received as a kind gift from Professor Lynda Bonewald (School of Dentistry, University of Missouri, Kansas City, MO, U.S.A.). The authors acknowledge the facilities and scientific and technical assistance of the Centre for Microscopy & Imaging at the National University of Ireland Galway (www.imaging.nuigalway.ie). The authors acknowledge the facilities and scientific and technical assistance of the Genomics and Screening Core at the National University of Ireland Galway, a facility that is funded by NUIG and the Irish Government’s Programme for Research in Third Level Institutions, Cycles 4 and 5, National Development Plan 2007–2013.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherNature Research (part of Springer Nature)en_IE
dc.relation.ispartofScientific Reportsen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectFLUID-FLOW STIMULATIONen_IE
dc.subjectFOCAL ADHESION KINASEen_IE
dc.subjectSTRAIN AMPLIFICATIONen_IE
dc.subjectBONE-CELLSen_IE
dc.subjectMECHANICAL-STRESSen_IE
dc.subjectGAP-JUNCTIONen_IE
dc.subjectEXPRESSIONen_IE
dc.subjectMODELen_IE
dc.subjectOSTEOPROTEGERINen_IE
dc.subjectRANKLen_IE
dc.titleEstrogen deficiency impairs integrin αvβ3-mediated mechanosensation by osteocytes and alters osteoclastogenic paracrine signallingen_IE
dc.typeArticleen_IE
dc.date.updated2020-01-14T08:59:17Z
dc.identifier.doi10.1038/s41598-019-41095-3
dc.local.publishedsourcehttps://doi.org/10.1038/s41598-019-41095-3en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderEuropean Regional Development Funden_IE
dc.contributor.funderEuropean Research Councilen_IE
dc.internal.rssid16091866
dc.local.contactLaoise Mcnamara, Biomedical Engineering, Eng-3038, New Engineering Building, Nui Galway. 2251 Email: laoise.mcnamara@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/EC/FP7::SP2::ERC/336882/EU/Primary Cilium-Mediated Mesenchymal Stem Cell Mechanobiology in Bone/CILIAMECHANOBIOen_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI ERC Support Programme/13/ERC/L2864/IE/SFI ERC Support - Dr. David Hoey/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/en_IE
nui.item.downloads189


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland