Cited by 477Genetic and Kidney Cyst DiseasesBone Metabolism and DiseasesCellular Mechanics and Interactions

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Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism

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Malone, Amanda M. D., Anderson, Charles T., Tummala, Padmaja, Kwon, Ronald Y., Johnston, Tyler R., Stearns, Tim, Jacobs, Christopher R.·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0700636104PMC PMC1939687

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Abstract

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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10.1097/00006534-200301000-00037 · DOI

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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: Anderson, Charles T.
Tummala, Padmaja
Kwon, Ronald Y.
Johnston, Tyler R.
Stearns, Tim
Jacobs, Christopher R.
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
DOI: 10.1073/pnas.0700636104
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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Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism

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