Peer-Reviewed Journal Details
Mandatory Fields
Johnson, GP;Stavenschi, E;Eichholz, KF;Corrigan, MA;Fair, S;Hoey, DA
2018
November
Journal Of Cell Science
Mesenchymal stem cell mechanotransduction is cAMP dependent and regulated by adenylyl cyclase 6 and the primary cilium
Published
2 ()
Optional Fields
BONE-FORMATION SHEAR-STRESS OSTEOGENIC DIFFERENTIATION FLUID-FLOW ACTIVATION FORSKOLIN MAGNITUDE FREQUENCY MARROW KINASE
131
Mechanical loading is a potent stimulus of bone adaptation, requiring the replenishment of the osteoblast from a progenitor population. One such progenitor is themesenchymal stemcell (MSC), which undergoes osteogenic differentiation in response to oscillatory fluid shear. Yet, the mechanism mediating stem cell mechanotransduction, and thus the potential to target this therapeutically, is poorly understood. In this study, we demonstrate that MSCs utilise cAMP as a second messenger in mechanotransduction, which is required for flow-mediated increases in osteogenic gene expression. Furthermore, we demonstrate that this mechanosignalling is dependent on the primary cilium and the ciliary localised adenylyl cyclase 6. Finally, we also demonstrate that this mechanotransduction mechanism can be targeted therapeutically to enhance cAMP signalling and early osteogenic signalling, mimicking the beneficial effect of physical loading. Our findings therefore demonstrate a novel mechanism of MSC mechanotransduction that can be targeted therapeutically, demonstrating a potential mechanotherapeutic for bone-loss diseases such as osteoporosis.This article has an associated First Person interview with the first author of the paper.
CAMBRIDGE
0021-9533
10.1242/jcs.222737
Grant Details