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Connexin Gap Junctions and Hemichannels Link Oxidative Stress to Skeletal Physiology and Pathology

  • Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The goal of this review is to provide an overview of the impact and underlying mechanism of oxidative stress on connexin channel function, and their roles in skeletal aging, estrogen deficiency, and glucocorticoid excess associated bone loss.

Recent Findings

Connexin hemichannel opening is increased under oxidative stress conditions, which confers a cell protective role against oxidative stress-induced cell death. Oxidative stress acts as a key contributor to aging, estrogen deficiency, and glucocorticoid excess-induced osteoporosis and impairs osteocytic network and connexin gap junction communication.

Summary

This paper reviews the current knowledge for the role of oxidative stress and connexin channels in the pathogenesis of osteoporosis and physiological and pathological responses of connexin channels to oxidative stress. Oxidative stress decreases osteocyte viability and impairs the balance of anabolic and catabolic responses. Connexin 43 (Cx43) channels play a critical role in bone remodeling, mechanotransduction, and survival of osteocytes. Under oxidative stress conditions, there is a consistent reduction of Cx43 expression, while the opening of Cx43 hemichannels protects osteocytes against cell injury caused by oxidative stress.

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Acknowledgments

We thank Dr. Eduardo Cardenas at UTHSCSA for critical reading and editing of the paper.

Funding

This work was supported by the National Institutes of Health (NIH) (grant: AR072072) and Welch Foundation (grant: AQ-1507) (to J.X.J.).

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  1. Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA

    Rui Hua, Jingruo Zhang, Manuel A. Riquelme & Jean X. Jiang

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  1. Rui Hua
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  2. Jingruo Zhang
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Correspondence to Jean X. Jiang.

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Rui Hua, Jingruo Zhang, Manuel A. Riquelme, and Jean X. Jiang declare no conflict of interest.

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This article is part of the Topical Collection on Skeletal Biology and Regulation

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Hua, R., Zhang, J., Riquelme, M.A. et al. Connexin Gap Junctions and Hemichannels Link Oxidative Stress to Skeletal Physiology and Pathology. Curr Osteoporos Rep 19, 66–74 (2021). https://doi.org/10.1007/s11914-020-00645-9

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