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TRPV4-mediates oscillatory fluid shear mechanotransduction in mesenchymal stem cells in part via the primary cilium

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Show simple item record Corrigan, Michele A. Johnson, Gillian P. Stavenschi, Elena Riffault, Mathieu Labour, Marie-Noëlle Hoey, David A. 2018-03-16T10:05:53Z 2018-03-16T10:05:53Z 2018
dc.description peer-reviewed en_US
dc.description.abstract Skeletal homeostasis requires the continued replenishment of the bone forming osteoblast from a mesenchymal stem cell (MSC) population, a process that has been shown to be mechanically regulated. However, the mechanisms by which a biophysical stimulus can induce a change in biochemical signaling, mechanotransduction, is poorly understood. As a precursor to loading-induced bone formation, deciphering the molecular mechanisms of MSC osteogenesis is a critical step in developing novel anabolic therapies. Therefore, in this study we characterize the expression of the mechanosensitive calcium channel Transient Receptor Potential subfamily V member 4 (TRPV4) in MSCs and demonstrate that TRPV4 localizes to areas of high strain, specifically the primary cilium. We demonstrate that TRPV4 is required for MSC mechanotransduction, mediating oscillatory fluid shear induced calcium signaling and early osteogenic gene expression. Furthermore, we demonstrate that TRPV4 can be activated pharmacologically eliciting a response that mirrors that seen with mechanical stimulation. Lastly, we show that TRPV4 localization to the primary cilium is functionally significant, with MSCs with defective primary cilia exhibiting an inhibited osteogenic response to TRPV4 activation. Collectively, this data demonstrates a novel mechanism of stem cell mechanotransduction, which can be targeted therapeutically, and further highlights the critical role of the primary cilium in MSC biology. en_US
dc.language.iso eng en_US
dc.publisher Nature Publishing Group en_US
dc.relation.ispartofseries Scientific Reports;8:3824
dc.subject TRPV4 en_US
dc.subject oscillatory fluid en_US
dc.subject mesenchymal stem cells (MSC) en_US
dc.subject cilium en_US
dc.title TRPV4-mediates oscillatory fluid shear mechanotransduction in mesenchymal stem cells in part via the primary cilium en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1038/s41598-018-22174-3
dc.contributor.sponsor ERC en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid #336882 en_US
dc.relation.projectid 13/ERC/L2864 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2741970

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