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Article
Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis
Journal of Molecular Medicine
  • Paxton M. Moon, Western University
  • Silvia Penuela, Western University
  • Kevin Barr, Western University
  • Sami Khan, Western University
  • Christopher L. Pin, Western University
  • Ian Welch, The University of British Columbia
  • Mukundan Attur, NYU Langone Orthopedic Hospital
  • Steven B. Abramson, NYU Langone Orthopedic Hospital
  • Dale W. Laird, Western University
  • Frank Beier, Western University
Document Type
Article
Publication Date
8-25-2015
URL with Digital Object Identifier
10.1007/s00109-015-1311-1
Abstract

© 2015, Springer-Verlag Berlin Heidelberg. Abstract: Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no overt phenotype and had no obvious effect on early skeletal development. Mice lacking Panx3 specifically in the cartilage and global Panx3 knockout mice were markedly resistant to the development of OA following destabilization of medial meniscus surgery. These data indicate a specific catabolic role of Panx3 in articular cartilage and identify Panx3 as a potential therapeutic target for OA. Lastly, while Panx1 has been linked to over a dozen human pathologies, this is the first in vivo evidence for a role of Panx3 in disease. Key message: Panx3 is localized to cartilage lesions in mice and humans.Global Panx3 deletion does not result in any developmental abnormalities.Mice lacking Panx3 are resistant to the development of osteoarthritis.Panx3 is a novel therapeutic target for the treatment of osteoarthritis.

Notes

This is a post-peer-review, pre-copyedit version of an article published in Journal of Molecular Medicine.

The final authenticated version is available online at: doi:10.1007/s00109-015-1311-1.

Published in final edited form as: J Mol Med (Berl). 2015 August; 93(8): 845–856. doi:10.1007/s00109-015-1311-1.

Citation Information
Paxton M. Moon, Silvia Penuela, Kevin Barr, Sami Khan, et al.. "Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis" Journal of Molecular Medicine Vol. 93 Iss. 8 (2015) p. 845 - 856
Available at: http://works.bepress.com/frank-beier/16/