Primary cilia act as mechanosensors during bone healing around an implant.
The primary cilium is an organelle that senses cues in a cell's local environment. Some of these cues constitute molecular signals; here, we investigate the extent to which primary cilia can also sense mechanical stimuli. We used a conditional approach to delete Kif3a in pre-osteoblasts and then employed a motion device that generated a spatial distribution of strain around an intra-osseous implant positioned in the mouse tibia. We correlated interfacial strain fields with cell behaviors ranging from proliferation through all stages of osteogenic differentiation. We found that peri-implant cells in the Col1Cre;Kif3a(fl/fl) mice were unable to proliferate in response to a mechanical stimulus, failed to deposit and then orient collagen fibers to the strain fields caused by implant displacement, and failed to differentiate into bone-forming osteoblasts. Collectively, these data demonstrate that the lack of a functioning primary cilium blunts the normal response of a cell to a defined mechanical stimulus. The ability to manipulate the genetic background of peri-implant cells within the context of a whole, living tissue provides a rare opportunity to explore mechanotransduction from a multi-scale perspective.
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. Pleucht@stanford.edu
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P
Leucht
S D
SD
Monica
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S
Temiyasathit
K
K
Lenton
A
A
Manu
M T
MT
Longaker
C R
CR
Jacobs
R L
RL
Spilker
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H
Guo
J B
JB
Brunski
J A
JA
Helms
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002923:Cilia / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D016547:Kinesins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D016012:Poisson Distribution; D019736:Prostheses and Implants; D044968:Regenerative Medicine / Q000379:methods; D015398:Signal Transduction; D013314:Stress, Mechanical; D013977:Tibia / Q000473:pathology
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C490202:Kif3a protein, mouse; D016547:Kinesins