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J Biol Chem. 2008 Sep 26;283(39):26374-82. doi: 10.1074/jbc.M803136200. Epub 2008 Jul 31.

Adaptation of connexin 43-hemichannel prostaglandin release to mechanical loading.

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  • 1Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.

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, PGE(2), a crucial factor for bone formation in response to anabolic loading. We show here that the opening of hemichannels and release of PGE(2) 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 PGE(2) 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.

PMID:
18676366
[PubMed - indexed for MEDLINE]
PMCID:
PMC2546557
Free PMC Article
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