Document Detail

Connexin 43 channels protect osteocytes against oxidative stress-induced cell death.
MedLine Citation:
PMID:  23456878     Owner:  NLM     Status:  MEDLINE    
The increased osteocyte death by oxidative stress (OS) during aging is a major cause contributing to the impairment of bone quality and bone loss. However, the underlying molecular mechanism is largely unknown. Here, we show that H₂O₂ induced cell death of primary osteocytes and osteocytic MLO-Y4 cells, and also caused dose-dependent decreased expression of gap junction and hemichannel-forming connexin 43 (Cx43). The decrease of Cx43 expression was also demonstrated with the treatment of other oxidants, rotenone and menadione. Antioxidant reversed the effects of oxidants on Cx43 expression and osteocyte cell death. Cx43 protein was also much lower in the osteocytes from 20-month-old as opposed to the 5-week-old or 20-week old mice. Dye transfer assay showed that H₂O₂ reduced the gap junction intercellular communication (GJIC). In contrast to the effect on GJIC, there was a dose-dependent increase of hemichannel function by H₂O₂, which was correlated with the increased cell surface expression of Cx43. Cx43(E2) antibody, an antibody that specifically blocks Cx43 hemichannel activity but not gap junctions, completely blocked dye uptake induced by H₂O₂ and further exacerbated H₂O₂-induced osteocytic cell death. In addition, knockdown of Cx43 expression by small interfering RNA (siRNA) increased the susceptibility of the cells to OS-induced death. Together, our study provides a novel cell protective mechanism mediated by osteocytic Cx43 channels against OS.
Rekha Kar; Manuel A Riquelme; Sherry Werner; Jean X Jiang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  28     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-19     Completed Date:  2013-11-04     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1611-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
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MeSH Terms
Cell Communication / drug effects,  genetics
Cell Death / drug effects
Cell Line
Connexin 43 / biosynthesis*,  genetics
Gap Junctions / genetics,  metabolism
Gene Expression Regulation / drug effects*,  genetics
Hydrogen Peroxide / pharmacology*
Osteocytes / cytology,  metabolism*
Oxidants / pharmacology*
Oxidative Stress / drug effects*,  genetics
Grant Support
Reg. No./Substance:
0/Connexin 43; 0/GJA1 protein, mouse; 0/Oxidants; BBX060AN9V/Hydrogen Peroxide

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