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Mesenchymal stem cell mechanotransduction is cAMP dependent and regulated by adenylyl cyclase 6 and the primary cilium

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posted on 2023-01-11, 14:16 authored by Gillian P. Johnson, Elena Stavenschi, Kian F. Eichholz, Michele A. Corrigan, Sean FairSean Fair, David A. Hoey
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.

Funding

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History

Publication

Journal of Cell Science;131

Publisher

Company of Biologists

Note

peer-reviewed

Other Funding information

ERC, IRC, SFI

Language

English

Department or School

  • Biological Sciences
  • School of Engineering

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