KEY POINTS * Multiple connexins are expressed in musculoskeletal tissues, including in joints * Gap-junctional intercellular communication contributes to interconnected cell syncytium, which

connect various cell types within joints * Connexin dysfunction might contribute to joint disease * Emerging data suggest that connexins might be novel targets for treating joint disease

ABSTRACT Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels,

releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions,

but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that

connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional

channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and

highlights the therapeutic potential of connexins. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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276–285 (2014). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS The work of the authors is supported by grants from the NIH, National Institute of Arthritis and

Musculoskeletal and Skin Diseases, R01AR068132-17 (to H.J.D.), R01AR 064255–05 (to D.C.G.) and a Virginia Commonwealth University School of Engineering Foundation Endowment (to H.J.D.).

AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biomedical Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, 23284, Virginia, USA Henry J. Donahue *

Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California at Davis, One Shields Avenue, Davis, 95616, California, USA Roy W. Qu & Damian

C. Genetos Authors * Henry J. Donahue View author publications You can also search for this author inPubMed Google Scholar * Roy W. Qu View author publications You can also search for this

author inPubMed Google Scholar * Damian C. Genetos View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors researched the data for the

article, provided substantial contributions to discussions of its content, wrote the article and reviewed and/or edited the manuscript before submission. CORRESPONDING AUTHOR Correspondence

to Henry J. Donahue. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2

POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 GLOSSARY * Cre-lox recombination A site-specific recombinase technology that is used to produce deletions, insertions, translocations

and inversions at specific sites in the DNA of cells. * Anabolic loading Mechanical loading that increases the abundance of bone. * Pannexin channels A family of vertebrate proteins that

predominantly exist as large transmembrane channels connecting the intracellular and extracellular space. * Chondron pellets Groups of chondrocytes and their adjacent pericellular

environment that have been centrifuged to form dense pellets. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Donahue, H., Qu, R. & Genetos, D. Joint

diseases: from connexins to gap junctions. _Nat Rev Rheumatol_ 14, 42–51 (2018). https://doi.org/10.1038/nrrheum.2017.204 Download citation * Published: 19 December 2017 * Issue Date:

January 2018 * DOI: https://doi.org/10.1038/nrrheum.2017.204 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

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