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Vol. 16, Issue 7, 3100-3106, July 2005
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* Department of Biochemistry, University of Texas Health Science Center, San Antonio, TX 78229-3900;
Department of Radiology, University of Texas Health Science Center, San Antonio, TX 78229-3900; and
Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, MO 64108
Submitted October 19, 2004;
Revised March 18, 2005;
Accepted April 8, 2005
Monitoring Editor: Asma Nusrat
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 
-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.
Abbreviations used: -GA, 18 -glycyrrhetinic acid; Cx43, connexin 43; DIDS, 4,4'-diisothiocyanatostilbene 2,2'-disulfonate; LY, Lucifer yellow; oATP, oxidized ATP; ODN, oligodeoxynucleotide; PGE2, prostaglandin E2; RD, rhodamine dextran.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Jean X. Jiang (jiangj{at}uthscsa.edu).
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