Abstract
Bone density loss is a major concern for astronauts in space, largely due to altered mechanical stimuli in microgravity. These changes are thought to impact bone cells by directly affecting musculoskeletal cell physiology and disrupting mechanosensing and mechanotransduction pathways. This review focuses on the role of the primary cilium, a small, non-motile cellular structure, involved in these processes. Previously underestimated, the primary cilium is now known to act as a mechano- and chemo-sensor on the surface of most vertebrate cells, transmitting signals via multiple intracellular pathways. The primary cilium senses the extracellular fluid flow and its dynamic changes in physiological and pathological conditions, which may include exposure to microgravity, connecting its inactivation to bone density loss. This systematic review will compile and analyze current data on how weightlessness affects the mechanosensing functions of the primary cilium and its role in bone homeostasis disruption.
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Acknowledgements
This study was partially funded by Università Cattolica del Sacro Cuore “linea D.1 and linea D.3.1” to W.L. The authors acknowledge the Regenerative Medicine Research Center (CROME) of the Università Cattolica del Sacro Cuore.
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Conceptualization: D.D.T. and W.L.; writing—original draft preparation: D.D.T., F.T., L.P.; writing review and editing: W.L., F.T., A.A., A.M., and L.D.P.; funding acquisition: A.M., W.L., and O.P. All authors have read and agreed to the published version of the manuscript.
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Tosi, D.D., Tiberio, F., Di Pietro, L. et al. Effects of microgravity mechanotransduction in bone tissue and cells: systematic review on primary cilium-dependent mechanisms. npj Microgravity (2026). https://doi.org/10.1038/s41526-025-00556-y
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DOI: https://doi.org/10.1038/s41526-025-00556-y
