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Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling

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dc.contributor.author Johnson, Gillian P.
dc.contributor.author Faair, Sean
dc.contributor.author Hoey, David A.
dc.date.accessioned 2021-02-18T14:07:00Z
dc.date.available 2021-02-18T14:07:00Z
dc.date.issued 2021
dc.identifier.uri http://hdl.handle.net/10344/9796
dc.description peer-reviewed en_US
dc.description.abstract The benefits of physical loading to skeletal mass are well known. The primary cilium has emerged as an important organelle in bone mechanobiology/mechanotransduction, particularly in mesenchymal stem/stromal cells, yet the molecular mechanisms of cilium mechanotransduction are poorly understood. In this study, we demonstrate that Gpr161 is a mechanoresponsive GPCR, that localises to the cilium, and is involved in fluid shear-induced cAMP signalling and downstream osteogenesis. This Gpr161-mediated mechanotransduction is dependent on IFT88/cilium and may act through adenylyl cyclase 6 (AC6) to regulate cAMP and MSC osteogenesis. Moreover, we demonstrate that Hh signalling is positively associated with osteogenesis and that Hh gene expression is mechanically regulated and required for loading-induced osteogenic differentiation through a mechanism that involves IFT88, Gpr161, AC6, and cAMP. Therefore, we have delineated a molecular mechanism of MSC mechanotransduction which likely occurs at the cilium, leading to MSC osteogenesis, highlighting novel mechanotherapeutic targets to enhance osteogenesis. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation 336882 en_US
dc.relation.ispartofseries Bone;145, 115846
dc.subject bone en_US
dc.subject osteogenesis en_US
dc.subject oscillatory fluid shear en_US
dc.subject mesenchymal stem/stromal cell en_US
dc.title Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling 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 10.1016/j.bone.2021.115846
dc.contributor.sponsor European Union (EU) en_US
dc.contributor.sponsor ERC en_US
dc.contributor.sponsor IRC en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid 336882 en_US
dc.relation.projectid GOIPG/2014/1463 en_US
dc.relation.projectid 13/ERC/L2864 en_US
dc.relation.projectid 19/FFP/6533 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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