dc.contributor.author | Geoghegan, Ivor P. | |
dc.contributor.author | Hoey, David A. | |
dc.contributor.author | McNamara, Laoise M. | |
dc.date.accessioned | 2020-01-14T09:15:24Z | |
dc.date.available | 2020-01-14T09:15:24Z | |
dc.date.issued | 2019-03-15 | |
dc.identifier.citation | Geoghegan, 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/s41598-019-41095-3 | en_IE |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10379/15703 | |
dc.description.abstract | The 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.sponsorship | This 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.format | application/pdf | en_IE |
dc.language.iso | en | en_IE |
dc.publisher | Nature Research (part of Springer Nature) | en_IE |
dc.relation.ispartof | Scientific Reports | en |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | FLUID-FLOW STIMULATION | en_IE |
dc.subject | FOCAL ADHESION KINASE | en_IE |
dc.subject | STRAIN AMPLIFICATION | en_IE |
dc.subject | BONE-CELLS | en_IE |
dc.subject | MECHANICAL-STRESS | en_IE |
dc.subject | GAP-JUNCTION | en_IE |
dc.subject | EXPRESSION | en_IE |
dc.subject | MODEL | en_IE |
dc.subject | OSTEOPROTEGERIN | en_IE |
dc.subject | RANKL | en_IE |
dc.title | Estrogen deficiency impairs integrin αvβ3-mediated mechanosensation by osteocytes and alters osteoclastogenic paracrine signalling | en_IE |
dc.type | Article | en_IE |
dc.date.updated | 2020-01-14T08:59:17Z | |
dc.identifier.doi | 10.1038/s41598-019-41095-3 | |
dc.local.publishedsource | https://doi.org/10.1038/s41598-019-41095-3 | en_IE |
dc.description.peer-reviewed | peer-reviewed | |
dc.contributor.funder | Science Foundation Ireland | en_IE |
dc.contributor.funder | European Regional Development Fund | en_IE |
dc.contributor.funder | European Research Council | en_IE |
dc.internal.rssid | 16091866 | |
dc.local.contact | Laoise Mcnamara, Biomedical Engineering, Eng-3038, New Engineering Building, Nui Galway. 2251 Email: laoise.mcnamara@nuigalway.ie | |
dc.local.copyrightchecked | Yes | |
dc.local.version | ACCEPTED | |
dcterms.project | info:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/ | en_IE |
dcterms.project | info:eu-repo/grantAgreement/EC/FP7::SP2::ERC/336882/EU/Primary Cilium-Mediated Mesenchymal Stem Cell Mechanobiology in Bone/CILIAMECHANOBIO | en_IE |
dcterms.project | info:eu-repo/grantAgreement/SFI/SFI ERC Support Programme/13/ERC/L2864/IE/SFI ERC Support - Dr. David Hoey/ | en_IE |
dcterms.project | info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2278/IE/Advanced Materials and BioEngineering Research Centre (AMBER)/ | en_IE |
nui.item.downloads | 227 | |