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

The benefits of physical loading to skeletal mass are well known. primary cilium has emerged as an important organelle in bone mechanobiology/mechanotransduction, particularly mesenchymal stem/stromal cells, yet the molecular mechanisms mechanotransduction poorly understood. In this study, we demonstrate that Gpr161 is a mechanoresponsive GPCR, localises cilium, and involved fluid shear-induced cAMP signalling downstream osteogenesis. This Gpr161-mediated dependent on IFT88/cilium may act through adenylyl cyclase 6 (AC6) regulate MSC Moreover, Hh positively associated with osteogenesis gene expression mechanically regulated required for loading-induced osteogenic differentiation mechanism involves IFT88, Gpr161, AC6, cAMP. Therefore, have delineated which likely occurs at leading osteogenesis, highlighting novel mechanotherapeutic targets enhance