Mechanosensing by the primary cilium: Deletion of Kif3a reduces bone formation due to loading

Sara Temiyasathit, W. Joyce Tang, Philipp Leucht, Charles T. Anderson, Stefanie D. Monica, Alesha B. Castillo, Jill A. Helms, Tim Stearns, Christopher R. Jacobs

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Primary cilia, solitary microtubule-based structures that grow from the centriole and extend into the extracellular space, have increasingly been implicated as sensors of a variety of biochemical and biophysical signals. Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation. We propose that primary cilia are also important in mechanically regulated bone formation in adults and that their malfunction could play a role in complex multi-factorial bone diseases, such as osteoporosis. In this study, we generated mice with an osteoblast- and osteocyte-specific knockout of Kif3a, a subunit of the kinesin II intraflagellar transport (IFT) protein; IFT is required for primary cilia formation, maintenance, and function. These Colα1(I) 2.3-Cre;Kif3a fl/fl mice exhibited no obvious morphological skeletal abnormalities. Skeletally mature Colα1(I) 2.3-Cre;Kif3a fl/fl and control mice were exposed to 3 consecutive days of cyclic axial ulna loading, which resulted in a significant increase in bone formation in both the conditional knockouts and controls. However, Colα1(I) 2.3-Cre;Kif3a fl/fl mice did exhibit decreased formation of new bone in response to mechanical ulnar loading compared to control mice. These results suggest that primary cilia act as cellular mechanosensors in bone and that their function may be critical for the regulation of bone physiology due to mechanical loading in adults.

Original languageEnglish (US)
Article numbere33368
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 12 2012

Fingerprint

Cilia
cilia
bone formation
Osteogenesis
Bone
mice
bones
Centrioles
bone diseases
Bone and Bones
Osteocytes
kinesin
Ulna
centrioles
ulna
osteoblasts
extracellular space
Bone Diseases
osteoporosis
transport proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Temiyasathit, S., Tang, W. J., Leucht, P., Anderson, C. T., Monica, S. D., Castillo, A. B., ... Jacobs, C. R. (2012). Mechanosensing by the primary cilium: Deletion of Kif3a reduces bone formation due to loading. PLoS One, 7(3), [e33368]. https://doi.org/10.1371/journal.pone.0033368
Temiyasathit, Sara ; Tang, W. Joyce ; Leucht, Philipp ; Anderson, Charles T. ; Monica, Stefanie D. ; Castillo, Alesha B. ; Helms, Jill A. ; Stearns, Tim ; Jacobs, Christopher R. / Mechanosensing by the primary cilium : Deletion of Kif3a reduces bone formation due to loading. In: PLoS One. 2012 ; Vol. 7, No. 3.
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Temiyasathit, S, Tang, WJ, Leucht, P, Anderson, CT, Monica, SD, Castillo, AB, Helms, JA, Stearns, T & Jacobs, CR 2012, 'Mechanosensing by the primary cilium: Deletion of Kif3a reduces bone formation due to loading', PLoS One, vol. 7, no. 3, e33368. https://doi.org/10.1371/journal.pone.0033368

Mechanosensing by the primary cilium : Deletion of Kif3a reduces bone formation due to loading. / Temiyasathit, Sara; Tang, W. Joyce; Leucht, Philipp; Anderson, Charles T.; Monica, Stefanie D.; Castillo, Alesha B.; Helms, Jill A.; Stearns, Tim; Jacobs, Christopher R.

In: PLoS One, Vol. 7, No. 3, e33368, 12.03.2012.

Research output: Contribution to journalArticle

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T2 - Deletion of Kif3a reduces bone formation due to loading

AU - Temiyasathit, Sara

AU - Tang, W. Joyce

AU - Leucht, Philipp

AU - Anderson, Charles T.

AU - Monica, Stefanie D.

AU - Castillo, Alesha B.

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AU - Stearns, Tim

AU - Jacobs, Christopher R.

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