Mechanical Strain Opens Connexin 43 Hemichannels in Osteocytes: A Novel Mechanism for the Release of Prostaglandin
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Published:2005-07
Issue:7
Volume:16
Page:3100-3106
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ISSN:1059-1524
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Container-title:Molecular Biology of the Cell
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language:en
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Short-container-title:MBoC
Author:
Cherian Priscilla P.1, Siller-Jackson Arlene J.1, Gu Sumin1, Wang Xin1, Bonewald Lynda F.2, Sprague Eugene3, Jiang Jean X.1
Affiliation:
1. Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900 2. Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, MO 64108 3. Department of Radiology, University of Texas Health Science Center, San Antonio, TX 78229-3900
Abstract
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 E2 (PGE2). Cells plated at lower densities release more PGE2 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 P2X7 and the prostaglandin transporter PGT, had no effect on PGE2 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 PGE2 in response to mechanical strain.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
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