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One such mechanical stimulus generated is hydrostatic pressure (HP); however, the effect of HP on mesenchymal stem cells (MSCs) and the mechanotransduction mechanisms utilized by these cells to sense this stimulus are yet to be fully elucidated. In this study, we demonstrate that cyclic HP is a potent mediator of cytoskeletal reorganization and increases in osteogenic responses in MSCs. In particular, we demonstrate that the intermediate filament (IF) network undergoes breakdown and reorganization with centripetal translocation of IF bundles toward the perinuclear region. Furthermore, we show for the first time that this IF remodeling is required for loading\u2010induced MSC osteogenesis, revealing a novel mechanism of MSC mechanotransduction. In addition, we demonstrate that chemical disruption of IFs with withaferin A induces a similar mechanism of IF breakdown and remodeling as well as a subsequent increase in osteogenic gene expression in MSCs, exhibiting a potential mechanotherapeutic effect to enhance MSC osteogenesis. This study therefore highlights a novel mechanotransduction mechanism of pressure\u2010induced MSC osteogenesis involving the understudied cytoskeletal structure, the IF, and demonstrates a potential new therapy to enhance bone formation in bone\u2010loss diseases such as osteoporosis.\u2014Stavenschi, E., Hoey, D. A. Pressure\u2010induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling. FASEB J. 33, 4178\u20134187 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801474rr","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T12:35:19Z","timestamp":1544790919000},"page":"4178-4187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pressure\u2010induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling"],"prefix":"10.1096","volume":"33","author":[{"given":"Elena","family":"Stavenschi","sequence":"first","affiliation":[{"name":"Trinity Centre for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical and Manufacturing Engineering School of Engineering Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Hoey","sequence":"additional","affiliation":[{"name":"Trinity Centre for Bioengineering Trinity Biomedical Sciences Institute Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical and Manufacturing Engineering School of Engineering Trinity College Dublin  Dublin Ireland"},{"name":"Department of Mechanical, Aeronautical, and Biomedical Engineering University of Limerick  Limerick Ireland"},{"name":"Advanced Materials and Bioengineering Research Centre Trinity College Dublin Royal College of Surgeons in Ireland (RCSI)  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bioeng.8.061505.095721"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.06.030"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.74"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-014-9573-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-276402"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.17485\/ijst\/2018\/v11i15\/121405"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9290(03)00127-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22118"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18089-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.02.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650071406"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(91)90381-V"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199702)170:2<174::AID-JCP9>3.0.CO;2-L"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(95)00097-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-1025-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-008-0038-2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12195-014-0329-8"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2012.0014"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.37.032807.125912"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.59.1.575"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20234"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004180100325"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.09.109"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00352.2005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/cm.21183","article-title":"Oscillatory fluid flow influences primary cilia and microtubule mechanics","volume":"71","author":"Espinha L. 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