Journal
EUROPEAN CELLS & MATERIALS
Volume 33, Issue -, Pages 158-168Publisher
AO RESEARCH INSTITUTE DAVOS-ARI
DOI: 10.22203/eCM.v033a12
Keywords
Primary cilia; mechanosensitivity; fenoldopam; osteocyte
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Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institute of Health (NIAMS/NIH) [AR062177]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR062177] Funding Source: NIH RePORTER
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The primary cilium is a mechanosensor in a variety of mammalian cell types, initiating and directing intracellular signalling cascades in response to external stimuli. When primary cilia formation is disrupted, cells have diminished mechanosensitivity and an abrogated response to mechanical stimulation. Due to this important role, we hypothesised that increasing primary cilia length would enhance the downstream response and therefore, mechanosensitivity. To test this hypothesis, we increased osteocyte primary cilia length with fenoldopam and lithium and found that cells with longer primary cilia were more mechanosensitive. Furthermore, fenoldopam treatment potentiated adenylyl cyclase activity and was able to recover primary cilia form and sensitivity in cells with impaired cilia. This work demonstrates that modulating the structure of the primary cilium directly impacts cellular mechanosensitivity. Our results implicate cilium length as a potential therapeutic target for combating numerous conditions characterised by impaired cilia function.
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