Michael Longaker

Publication Details

  • Primary cilia act as mechanosensors during bone healing around an implant MEDICAL ENGINEERING & PHYSICS Leucht, P., Monica, S. D., Temiyasathit, S., Lenton, K., Manu, A., Longaker, M. T., Jacobs, C. R., Spilkere, R. L., Guo, H., Brunski, J. B., Helms, J. A. 2013; 35 (3): 392-402

    Abstract:

    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.

    View details for DOI 10.1016/j.medengphy.2012.06.005

    View details for Web of Science ID 000315931400013

    View details for PubMedID 22784673

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