Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 33, Pages 13325-13330Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700636104
Keywords
intracellular signaling; mechanotransduction; osteoblast; osteocyte; fluid flow
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Funding
- NIAMS NIH HHS [R01 AR045989, AR45989] Funding Source: Medline
- NIGMS NIH HHS [R01 GM052022] Funding Source: Medline
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Primary cilia are sensory organelles that 'translate extracellular chemical and mechanical cues into cellular responses. Bone is an exquisitely mechanosensitive organ, and its homeostasis depends on the ability of bone cells to sense and respond to mechanical stimuli. One such stimulus is dynamic fluid flow, which triggers biochemical and transcriptional changes in bone cells by an unknown mechanism. Here we report that bone cells possess primary cilia that project from the cell surface and deflect during fluid flow and that these primary cilia are required for osteogenic and bone resorptive responses to dynamic fluid flow. We also show that, unlike in kidney cells, primary cilia in bone translate fluid flow into cellular responses in bone cells independently of Ca2+ flux and stretch-activated ion channels. These results suggest that primary cilia might regulate homeostasis in diverse tissues by allowing mechanical signals to alter cellular activity via tissue-specific pathways. Our identification of a mechanism for mechanotranscluction in bone could lead to therapeutic approaches for combating bone loss due to osteoporosis and disuse.
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