Oscillating fluid flow activation of gap junction hemichannels induces atp release from MLO‐Y4 osteocytes
Open accessAbstract
Mechanical loads are required for optimal bone mass. One mechanism whereby mechanical loads are transduced into localized cellular signals is strain‐induced fluid flow through lacunae and canaliculi of bone. Gap junctions (GJs) between osteocytes and osteoblasts provides a mechanism whereby flow‐induced signals are detected by osteocytes and transduced to osteoblasts. We have demonstrated the importance of GJ and gap junctional intercellular communication (GJIC) in intracellular calcium and prostaglandin E 2 (PGE 2 ) increases in response to flow. Unapposed connexons, or hemichannels, are themselves functional and may constitute a novel mechanotransduction mechanism. Using MC3T3‐E1 osteoblasts and MLO‐Y4 osteocytes, we examined the time course and mechanism of hemichannel activation in response to fluid flow, the composition of the hemichannels, and the role of hemichannels in flow‐induced ATP release. We demonstrate that fluid flow activates hemichannels in MLO‐Y4, but not MC3T3‐E1, through a mechanism involving protein kinase C, which induces ATP and PGE 2 release.. J. Cell. Physiol. 212: 207–214, 2007. © 2007 Wiley‐Liss, Inc.
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Mechanical loading stimulates osteocytes to produce anabolic factors PGE2, PGI2, NO, and IGF-1.
“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 [183]
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References 72 · Cited by 328
Research works printed but not linked: 1
- [42]42. Li J, Liu D, Duncan RL, Turner CH. Osteogenesis after mechanical loading requires the P2X7 nucleotide receptor. J Bone Miner Res. 2004;19(Suppl 1):1032. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=J%20Bone%20Miner%20Res&title=Osteogenesis%20after%20mechanical%20loading%20requires%20the%20P2X7%20nucleotide%20receptor&author=J%20Li&author=D%20Liu&author=RL%20Duncan&author=CH%20Turner&volume=19&issue=Suppl%201&publication_year=2004&pages=1032&)]
- Authors
- Genetos, D. C., Kephart, C. J., Zhang, Y., Yellowley, C. E., & Donahue, H. J.
- Affiliations
- University of California, Davis (US)
- Pennsylvania State University (US)
- Corresponding author
- Donahue, Henry J.
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2007-04-26
- Volume
- 212
- Issue
- 1
- Pages
- 207-214
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC2929812
- OpenAlex
- W2083920483
- Cited by
- 328
- References
- 72
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 21 · 2023: 12 · 2022: 17 · 2021: 15 · 2020: 25 · 2019: 21 · 2018: 11 · 2017: 16 · 2016: 14 · 2015: 19 · 2014: 15 · 2013: 20 · 2012: 32
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Aeronautics and Space Administration
- National Institute on Aging (R01AG022305, AG-13087, AG22305, R01AG013087)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- gap junction hemichannels, fluid flow, mechanotransduction, osteocytes, MLO-Y4 cells, ATP release, prostaglandin E2, protein kinase C, connexins, gap junctional intercellular communication, bone mechanotransduction, osteoblasts
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Line, Osteocytes, Protein Kinase C, Dinoprostone, Gap Junctions, Connexin 43, Receptors, Purinergic P2, RNA, Small Interfering, Mice
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