Cited by 265Cellular Mechanics and InteractionsCell Adhesion Molecules ResearchBone Metabolism and Diseases

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A model for the role of integrins in flow induced mechanotransduction in osteocytes

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Wang, Yilin, McNamara, Laoise M., Schaffler, Mitchell B., Weinbaum, Sheldon·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0707246104PMC PMC2000405

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Abstract

A fundamental paradox in bone mechanobiology is that tissue-level strains caused by human locomotion are too small to initiate intracellular signaling in osteocytes. A cellular-level strain-amplification model previously has been proposed to explain this paradox. However, the molecular mechanism for initiating signaling has eluded detection because none of the molecules in this previously proposed model are known mediators of intracellular signaling. In this paper, we explore a paradigm and quantitative model for the initiation of intracellular signaling, namely that the processes are attached directly at discrete locations along the canalicular wall by β 3 integrins at the apex of infrequent, previously unrecognized canalicular projections. Unique rapid fixation techniques have identified these projections and have shown them to be consistent with other studies suggesting that the adhesion molecules are α v β 3 integrins. Our theoretical model predicts that the tensile forces acting on the integrins are <15 pN and thus provide stable attachment for the range of physiological loadings. The model also predicts that axial strains caused by the sliding of actin microfilaments about the fixed integrin attachments are an order of magnitude larger than the radial strains in the previously proposed strain-amplification theory and two orders of magnitude greater than whole-tissue strains. In vitro experiments indicated that membrane strains of this order are large enough to open stretch-activated cation channels.

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Authors: Wang, Y., McNamara, L. M., Schaffler, M. B., & Weinbaum, S.
Affiliations: The Graduate Center, CUNY (US)
Icahn School of Medicine at Mount Sinai (US)
ORCID: McNamara, Laoise M.
Schaffler, Mitchell B.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2007-10-02
Volume: 104
Issue: 40
Pages: 15941-15946
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0707246104
PMC: PMC2000405
OpenAlex: W2131107390
Cited by: 265
References: 50
Citations by year: 2026: 10 · 2025: 9 · 2024: 13 · 2023: 17 · 2022: 13 · 2021: 17 · 2020: 11 · 2019: 12 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 21 · 2012: 17
FWCI: 7.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: National Institutes of Health (AR41210)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41210, R01AR041210, AR 48699, R01AR048699)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords: osteocytes, mechanotransduction, CD61, integrin αvβ3, bone mechanobiology, strain amplification, intracellular signaling, stretch-activated cation channels
MeSH terms: Actins, Animals, Mice, Inbred C57BL, Models, Biological, Osteocytes, Integrins, Models, Animal, Mechanotransduction, Cellular, Mice

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A model for the role of integrins in flow induced mechanotransduction in osteocytes

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