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Mechanical Strain Opens Connexin 43 Hemichannels in Osteocytes: A Novel Mechanism for the Release of Prostaglandin
Open accessAbstract
Mechanosensing bone osteocytes express large amounts of connexin (Cx)43, the component of gap junctions; yet, gap junctions are only active at the small tips of their dendritic processes, suggesting another function for Cx43. Both primary osteocytes and the osteocyte-like MLO-Y4 cells respond to fluid flow shear stress by releasing intracellular prostaglandin E 2 (PGE 2 ). Cells plated at lower densities release more PGE 2 than cells plated at higher densities. This response was significantly reduced by antisense to Cx43 and by the gap junction and hemichannel inhibitors 18 β-glycyrrhetinic acid and carbenoxolone, even in cells without physical contact, suggesting the involvement of Cx43-hemichannels. Inhibitors of other channels, such as the purinergic receptor P2X 7 and the prostaglandin transporter PGT, had no effect on PGE 2 release. Cell surface biotinylation analysis showed that surface expression of Cx43 was increased by shear stress. Together, these results suggest fluid flow shear stress induces the translocation of Cx43 to the membrane surface and that unapposed hemichannels formed by Cx43 serve as a novel portal for the release of PGE 2 in response to mechanical strain.
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“For example, mechanical loading stimulates osteocyte to produce factors that exert anabolic action on bone such as PGE2, prostacyclin (PGI2), NO, and IGF-1 [181–184].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [182]
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Background
Metadata
- Authors
- Cherian, P. P., Siller-Jackson, A. J., Gu, S., Wang, X., Bonewald, L. F., Sprague, E., & Jiang, J. X.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Missouri–Kansas City (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2005-07
- Volume
- 16
- Issue
- 7
- Pages
- 3100-3106
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC1165395
- OpenAlex
- W2101299206
- Cited by
- 481
- References
- 39
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 18 · 2023: 15 · 2022: 17 · 2021: 23 · 2020: 22 · 2019: 25 · 2018: 15 · 2017: 23 · 2016: 21 · 2015: 23 · 2014: 40 · 2013: 27 · 2012: 31
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AQ‐1507, AR46798)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P01AR046798, AR 46798)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- 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
- Keywords
- connexin 43, hemichannels, osteocytes, prostaglandin E2 release, fluid shear stress, mechanotransduction, gap junctions, MLO-Y4 cells, 18β-glycyrrhetinic acid, carbenoxolone, cell surface translocation, bone mechanosensing
- MeSH terms
- Animals, Bone and Bones, Carbenoxolone, Cell Line, Cell Membrane, Cells, Cultured, Chickens, Dendrites, Glycyrrhetinic Acid, Microscopy, Fluorescence, Osteocytes, Prostaglandins, Stress, Mechanical, Blotting, Western, Oligonucleotides, Antisense, Gap Junctions, Connexin 43, Receptors, Purinergic P2, Biotinylation, Mice, Rats, Receptors, Purinergic P2X7
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