The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
A model for the role of integrins in flow induced mechanotransduction in osteocytes
Open accessAbstract
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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“Integrins play a mediating role in osteocyte-bone matrix interactions. These interactions are essential for the mechanosensitive function of these cells, whereby signals induced by tissue deformation are generated and amplified [136].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [136]
Citations
Cites
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Self-citationMechanotransduction in bone—role of the lacunocanalicular network
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Cited by
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Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
Biomechanics and Mechanobiology of Trabecular Bone: A Review
Oftadeh, R., Perez‐Viloria, M., Villa‐Camacho, J. C., Vaziri, A., & Nazarian, A. (2014) · Journal of Biomechanical Engineering · doi:10.1115/1.4029176 · Cited by 616
Mechanosensation and transduction in osteocytes
Klein-Nulend, J., Bakker, A. D., Bacabac, R. G., Vatsa, A., & Weinbaum, S. (2013) · Bone · doi:10.1016/j.bone.2012.10.013 · Cited by 528
Self-citationFernández, M., Abbah, S. A., McNamara, L. M., Zeugolis, D. I., Pandit, A. S., & Biggs, M. J. P. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.09.005 · Cited by 524
Self-citationCrockett, J. C., Rogers, M. J., Coxon, F. P., Hocking, L. J., & Helfrich, M. (2011) · Journal of Cell Science · doi:10.1242/jcs.063032 · Cited by 532
Metadata
- 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)
- 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
- 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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