Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism

Amanda M.D. Malone, Charles T. Anderson, Padmaja Tummala, Ronald Y. Kwon, Tyler R. Johnston, Tim Stearns, Christopher R. Jacobs

Research output: Contribution to journalArticle

306 Scopus citations

Abstract

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 mechanotransduction in bone could lead to therapeutic approaches for combating bone loss due to osteoporosis and disuse.

Original languageEnglish (US)
Pages (from-to)13325-13330
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number33
DOIs
StatePublished - Aug 14 2007

All Science Journal Classification (ASJC) codes

  • General

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