Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism.
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 Ca(2+) 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.
Palo Alto Veterans Administration Medical Center, Palo Alto, CA 94304, USA.
Amanda M D
AM
Malone
Charles T
CT
Anderson
Padmaja
P
Tummala
Ronald Y
RY
Kwon
Tyler R
TR
Johnston
Tim
T
Stearns
Christopher R
CR
Jacobs
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D040542:Mechanotransduction, Cellular; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism
D002118:Calcium; D017931:DNA Primers; D050396:TRPP Cation Channels