Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin

Priscilla P. Cherian, Arlene J. Siller-Jackson, Sumin Gu, Xin Wang, Lynda F. Bonewald, Eugene Sprague, Jean X. Jiang

Research output: Contribution to journalArticle

330 Scopus citations

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 (PGE 2). 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 PGE 2 in response to mechanical strain.

Original languageEnglish (US)
Pages (from-to)3100-3106
Number of pages7
JournalMolecular Biology of the Cell
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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