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dc.contributor.authorHoey, Daviden
dc.date.accessioned2021-06-01T16:47:21Z
dc.date.available2021-06-01T16:47:21Z
dc.date.issued2021en
dc.date.submitted2021en
dc.identifier.citationGeoghegan IP, McNamara LM, Hoey DA., Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes., Scientific reports, 11, 1, 2021, 9272en
dc.identifier.issn2045-2322en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/96519
dc.descriptionPUBLISHEDen
dc.description.abstractEstrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) and is associated with impaired focal adhesions (FAs) and a disrupted actin cytoskeleton. RANKL production is mediated by Hedgehog signalling in osteocytes, a signalling pathway associated with the primary cilium, and the ciliary structure is tightly coupled to the cytoskeleton. Therefore, the objective of this study was to investigate the role of the cilium and associated signalling in EW-mediated osteoclastogenic signalling in osteocytes. We report that EW leads to an elongation of the cilium and increase in Hedgehog and osteoclastogenic signalling. Significant trends were identified linking cilia elongation with reductions in cell area and % FA area/cell area, indicating that cilia elongation is associated with disruption of FAs and actin contractility. To verify this, we inhibited FA assembly via αvβ3 antagonism and inhibited actin contractility and demonstrated an elongated cilia and increased expression of Hh markers and Rankl expression. Therefore, our results suggest that the EW conditions associated with osteoporosis lead to a disorganisation of αvβ3 integrins and reduced actin contractility, which were associated with an elongation of the cilium, activation of the Hh pathway and osteoclastogenic paracrine signalling.en
dc.format.extent9272en
dc.language.isoenen
dc.relation.ispartofseriesScientific reportsen
dc.relation.ispartofseries11en
dc.relation.ispartofseries1en
dc.rightsYen
dc.subjectPost-menopausal osteoporosisen
dc.subjectRANKLen
dc.subjectIntegrinen
dc.subjectActin cytoskeletonen
dc.subjectCiliumen
dc.titleEstrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/dahoeyen
dc.identifier.rssinternalid230840en
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-021-88633-6en
dc.rights.ecaccessrightsopenAccess
dc.identifier.orcid_id0000-0001-5898-0409en


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