The DOI matches its Crossref record; 102 of the 102 references it cites were found in a registry or an index.
Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism
Open accessAbstract
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.
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“Osteocytes might sense FFSS through 1. “collagen hillocks”, which are collagen matrix projections in osteocyte canaliculi that directly link the matrix to osteocyte dendrites;29 2. β3 and β1 integrins, which participate to focal adhesion kinase (FAK) complex formation in osteocyte dendritic projections;30 3. primary cilia, which have a flow-sensing function that leads to increased osteoprotegerin”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [31]
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Cites
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Research works printed but not linked: 2
- GC Reilly, TR Haut, CE Yellowley, HJ Donahue, CR Jacobs Biorheology 40, 591–603 (2003).
- 10.1097/00006534-200301000-00037 · DOI
Cited by
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Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.320 · Cited by 2,287
Osteocytes, mechanosensing and Wnt signaling
Bonewald, L. F., & Johnson, M. L. (2008) · Bone · doi:10.1016/j.bone.2007.12.224 · Cited by 1,076
The Osteocyte: An Endocrine Cell … and More
Dallas, S. L., Prideaux, M., & Bonewald, L. F. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1026 · Cited by 1,042
Mechanical regulation of bone remodeling
Wang, L., You, X., Zhang, L., Zhang, C., & Zou, W. (2022) · Bone Research · doi:10.1038/s41413-022-00190-4 · Cited by 641
Mechanisms of Tooth Eruption and Orthodontic Tooth Movement
Wise, G. E., & King, G. J. (2008) · Journal of Dental Research · doi:10.1177/154405910808700509 · Cited by 581
Metadata
- Authors
- Malone, A. M. D., Anderson, C. T., Tummala, P., Kwon, R. Y., Johnston, T. R., Stearns, T., & Jacobs, C. R.
- Affiliations
- VA Palo Alto Health Care System (US)
- Stanford University (US)
- Stanford Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-08-14
- Volume
- 104
- Issue
- 33
- Pages
- 13325-13330
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1939687
- OpenAlex
- W2104440688
- Semantic Scholar
- f451262cfba816230b82b3b56064b900c1cc691a
- Cited by
- 477
- References
- 102
- Citations by year
- 2026: 17 · 2025: 11 · 2024: 9 · 2023: 20 · 2022: 21 · 2021: 24 · 2020: 32 · 2019: 21 · 2018: 19 · 2017: 26 · 2016: 33 · 2015: 27 · 2014: 24 · 2013: 36 · 2012: 40
- FWCI
- 15.53
- Type
- journal article
- Language
- en
- Update notices
- correction (2008-01-15)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Missouri
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM052022)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-45989, R01AR045989)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- primary cilia, mechanosensing, mechanotransduction, bone cells, fluid flow, osteogenic differentiation, bone resorption, calcium-independent signaling, stretch-activated channels, bone homeostasis, osteoporosis, disuse bone loss
- MeSH terms
- Animals, Base Sequence, Calcium, Cilia, Fluorescent Antibody Technique, Osteoblasts, Blotting, Western, 3T3 Cells, DNA Primers, Mechanotransduction, Cellular, TRPP Cation Channels, Mice
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