Johnson_2021_Primary.pdf (2.8 MB)
Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling
journal contribution
posted on 2022-10-03, 13:03 authored by Gillian P. Johnson, Sean FairSean Fair, David A. HoeyThe 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.
Funding
Study on Aerodynamic Characteristics Control of Slender Body Using Active Flow Control Technique
Japan Society for the Promotion of Science
Find out more...History
Publication
Bone;145, 115846Publisher
ElsevierNote
peer-reviewedOther Funding information
European Union (EU), ERC, IRC, SFILanguage
EnglishExternal identifier
Department or School
- School of Engineering
- Biological Sciences