Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading

Arlene J. Siller-Jackson, Sirisha Burra, Sumin Gu, Xuechun Xia, Lynda F. Bonewald, Eugene Sprague, Jean X. Jiang

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Bone tissues respond to mechanical loading/unloading regimens to accommodate (re)modeling requirements; however, the underlying molecular mechanism responsible for these responses is largely unknown. Previously, we reported that connexin (Cx) 43 hemichannels in mechanosensing osteocytes mediate the release of prostaglandin, PGE2, a crucial factor for bone formation in response to anabolic loading. We show here that the opening of hemichannels and release of PGE2 by shear stress were significantly inhibited by a potent antibody we developed that specifically blocks Cx43-hemichannels, but not gap junctions or other channels. The opening of hemichannels and release of PGE2 are magnitude-dependent on the level of shear stress. Insertion of a rest period between stress enhances this response. Hemichannels gradually close after 24 h of continuous shear stress corresponding with reduced Cx43 expression on the cell surface, thereby reducing any potential negative effects of channels staying open for extended periods. These data suggest that Cx43-hemichannel activity associated with PGE 2 release is adaptively regulated by mechanical loading to provide an effective means of regulating levels of extracellular signaling molecules responsible for initiation of bone (re)modeling.

Original languageEnglish (US)
Pages (from-to)26374-26382
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number39
DOIs
StatePublished - Sep 26 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Siller-Jackson, A. J., Burra, S., Gu, S., Xia, X., Bonewald, L. F., Sprague, E., & Jiang, J. X. (2008). Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading. Journal of Biological Chemistry, 283(39), 26374-26382. https://doi.org/10.1074/jbc.M803136200