HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 39, 26374-26382, September 26, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/39/26374    most recent M803136200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siller-Jackson, A. J. Articles by Jiang, J. X. Search for Related Content PubMed PubMed Citation Articles by Siller-Jackson, A. J. Articles by Jiang, J. X. Social Bookmarking                      What's this?

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^¶, and Jean X. Jiang¹

From the Departments of Biochemistry and ^¶Radiology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, and the Department of Oral Biology, School of Dentistry, University of Missouri, Kansas City, Missouri 64108

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 PGE₂ 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.

Received for publication, April 23, 2008 , and in revised form, July 30, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants F31 AR053468 (to A. J. S.-J.) and P01 AR46798 (to J. X. J., L. F. B., and E. S.). This work was also supported by the Welch Foundation Grant AQ-1507 (to J. X. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biochemistry, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Tel.: 210-567-3796; Fax: 210-695-8725; E-mail: jiangj{at}uthscsa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Lima, C. Niger, C. Hebert, and J. P. Stains Connexin43 Potentiates Osteoblast Responsiveness to Fibroblast Growth Factor 2 via a Protein Kinase C-Delta/Runx2-dependent Mechanism Mol. Biol. Cell, June 1, 2009; 20(11): 2697 - 2708. [Abstract] [Full Text] [PDF]