Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling.
Item Type:Journal Article
Citation:Johnson GP, Fair S, Hoey DA, Primary cilium-mediated MSC mechanotransduction is dependent on Gpr161 regulation of hedgehog signalling., Bone, 2021
BonePaper_TARA.pdf (Accepted for publication (author's copy) - Peer Reviewed) 1.096Mb
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.
Author: Hoey, David
Type of material:Journal Article
Availability:Full text available
Keywords:Bone, Osteogenesis, G protein coupled receptor, Mesenchymal Stem/Stromal Cell, Oscillatory fluid shear