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dc.contributor.authorDolan, Eimear B.
dc.contributor.authorHaugh, Margaret
dc.contributor.authorVoisin, Muriel C.
dc.contributor.authorTallon, David
dc.contributor.authorMcNamara, Laoise M.
dc.date.accessioned2016-12-13T10:29:14Z
dc.date.available2016-12-13T10:29:14Z
dc.date.issued2015-03-18
dc.identifier.citationDolan EB, Haugh MG, Voisin MC, Tallon D, McNamara LM (2015) Thermally Induced Osteocyte Damage Initiates a Remodelling Signaling Cascade. PLoS ONE 10(3): e0119652. doi:10.1371/journal.pone.0119652en_IE
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10379/6226
dc.description.abstractThermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanical stimuli and physical damage. However, whether heat-induced osteocyte damage can directly elicit bone remodelling has yet to be determined. This study establishes the link between osteocyte thermal damage and the remodeling cascade. We show that osteocytes directly exposed to thermal elevations (47 degrees C for 1 minute) become significantly apoptotic and alter the expression of osteogenic genes (Opg and Cox2). The Rankl/Opg ratio is consistently down-regulated, at days 1, 3 and 7 in MLO-Y4s heat-treated to 47 degrees C for 1 minute. Additionally, the pro-osteoblastogenic signaling marker Cox2 is significantly up-regulated in heat-treated MLO-Y4s by day 7. Furthermore, secreted factors from heat-treated MLO-Y4s administered to MSCs using a novel co-culture system are shown to activate pre-osteoblastic MSCs to increase production of the pro-osteoblastic differentiation marker, alkaline phosphatase (day 7, 14), and calcium deposition (day 21). Most interestingly, an initial pro-osteoclastogenic signaling response (increase Rankl and Rankl/Opg ratio at day 1) followed by later stage pro-osteoblastogenic signaling (down-regulation in Rankl and the Rankl/Opg ratio and an up-regulation in Opg and Cox2 by day 7) was observed in non-heat-treated MLO-Y4s in co-culture when these were exposed to the biochemicals produced by heat-treated MLO-Y4s. Taken together, these results elucidate the vital role of osteocytes in detecting and responding to thermal damage by means of thermally induced apoptosis followed by a cascade of remodelling responses.en_IE
dc.description.sponsorshipFunding from the National University of Ireland, Galway Fellowship Scheme, the National University of Ireland Travelling Scholarships in Engineering, the European Research Council (ERC) (under grant no. 258992;BONEMECHBIO).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherPublic Library of Scienceen_IE
dc.relation.ispartofPlos Oneen
dc.subjectBiomedical engineeringen_IE
dc.subjectMesenchymal stem cellsen_IE
dc.subjectMechanically stimulated osteocytesen_IE
dc.subjectGap junctionsen_IE
dc.subjectOsteogenic differentiationen_IE
dc.subjectOsteoclast differentiationen_IE
dc.subjectBone resorptionen_IE
dc.subjectIn vivoen_IE
dc.subjectApoptosisen_IE
dc.subjectProliferationen_IE
dc.subjectActivationen_IE
dc.titleThermally induced osteocyte damage initiates a remodelling signaling cascadeen_IE
dc.typeArticleen_IE
dc.date.updated2016-12-07T14:59:00Z
dc.identifier.doi10.1371/journal.pone.0119652
dc.local.publishedsourcehttp://dx.doi.org/ 10.1371/journal.pone.0119652en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid9392637
dc.local.contactLaoise Mcnamara, Biomedical Engineering, Eng-3038, New Engineering Building, Nui Galway. 2251 Email: laoise.mcnamara@nuigalway.ie
dc.local.copyrightcheckedNo
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