Potential role for a specialized β3 integrin‐based structure on osteocyte processes in bone mechanosensation
Open accessAbstract
Osteocyte processes are an order of magnitude more sensitive to mechanical loading than their cell bodies. The mechanisms underlying this remarkable mechanosensitivity are not clear, but may be related to the infrequent α V β 3 integrin sites where the osteocyte cell processes attach to canalicular walls. These sites develop dramatically elevated strains during load‐induced fluid flow in the lacunar‐canalicular system and were recently shown to be primary sites for osteocyte‐like MLO‐Y4 cell mechanotransduction. These α V β 3 integrin sites lack typical integrin transduction mechanisms. Rather, stimulation at these sites alters Ca 2+ signaling, ATP release and membrane potential. In the current studies, we tested the hypothesis that in authentic osteocytes in situ, key membrane proteins implicated in osteocyte mechanotransduction are preferentially localized at or near to β 3 integrin‐foci. We analyzed these spatial relationships in mouse bone osteocytes using immunohistochemistry combined with Structured Illumination Super Resolution Microscopy, a method that permits structural resolution at near electron microscopy levels in tissue sections. We discovered that the purinergic channel pannexin1, the ATP‐gated purinergic receptor P2 × 7R and the low voltage transiently opened T‐type calcium channel CaV3.2–1 all reside in close proximity to β 3 integrin attachment foci on osteocyte processes, suggesting a specialized mechanotransduction complex at these sites. We further confirmed this observation on isolated osteocytes in culture using STochasitc Optical Resonance Microscopy. These findings identify a possible structural basis for the unique mechanosensation and transduction capabilities of the osteocyte process. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:642–652, 2018.
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Osteocytes might sense FFSS through collagen hillocks, β3 and β1 integrins, primary cilia, connexin43, and mechanosensitive ion channels such as Piezo1.
“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 [30]
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- Authors
- Cabahug‐Zuckerman, P., Stout, R. F., Majeska, R. J., Thi, M. M., Spray, D. C., Weinbaum, S., & Schaffler, M. B.
- Affiliations
- Department of Biomedical Engineering The City College of New York New York New York
- Albert Einstein College of Medicine (US)
- City College of New York (US)
- Corresponding author
- Schaffler, Mitchell B.
- Venue
- Journal of Orthopaedic Research
- Publisher
- Wiley
- Published
- 2017-11-28
- Volume
- 36
- Issue
- 2
- Pages
- 642-652
- ISSN
- 0736-0266 (ISSN-L)
- 1554-527X
- PMC
- PMC5839970
- OpenAlex
- W2765810049
- Cited by
- 71
- References
- 74
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 17 · 2020: 8 · 2019: 9 · 2018: 4 · 2015: 1
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Orthopaedic Research® (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR041210, AR057139, AR060445)
- Albert Einstein College of Medicine, Yeshiva University (P30CA013330, SIG‐ 1S10OD18218‐1)
- National Institute of Neurological Disorders and Stroke (NS092466)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- osteocyte mechanotransduction, CD61, pannexin 1, P2X7 receptor, lacunar-canalicular system, fluid flow
- MeSH terms
- Animals, Cell Line, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Osteocytes, Receptors, Purinergic, Connexins, Calcium Channels, T-Type, Integrin beta3, Mechanotransduction, Cellular
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