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Journal of Molecular Medicine

, Volume 93, Issue 8, pp 845–856 | Cite as

Deletion of Panx3 Prevents the Development of Surgically Induced Osteoarthritis

  • Paxton M. Moon
  • Silvia Penuela
  • Kevin Barr
  • Sami Khan
  • Christopher L. Pin
  • Ian Welch
  • Mukundan Attur
  • Steven B. Abramson
  • Dale W. Laird
  • Frank Beier
Original Article

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.

Keywords

DMM Cartilage Mice Pannexin 3 Osteoarthritis 

Notes

Acknowledgments

This study was funded by a Canadian Institutes of Health Research operating grant (MOP130530) to DWL, FB, and SP. DWL and FB are supported by Canada Research Chair Awards. SBA and AM are supported in part by U.S. National Institutes of Health grant R01-AR054817.

Conflict of Interest

The authors declare that they have no competing interest.

Supplementary material

109_2015_1311_MOESM1_ESM.pdf (467 kb)
ESM 1 (PDF 466 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Paxton M. Moon
    • 1
  • Silvia Penuela
    • 2
  • Kevin Barr
    • 2
  • Sami Khan
    • 1
  • Christopher L. Pin
    • 1
    • 3
    • 4
    • 5
  • Ian Welch
    • 6
  • Mukundan Attur
    • 7
  • Steven B. Abramson
    • 7
  • Dale W. Laird
    • 1
    • 2
  • Frank Beier
    • 1
    • 5
  1. 1.Departments of Physiology and PharmacologyUniversity of Western OntarioLondonCanada
  2. 2.Anatomy and Cell BiologyUniversity of Western OntarioLondonCanada
  3. 3.PaediatricsUniversity of Western OntarioLondonCanada
  4. 4.OncologyUniversity of Western OntarioLondonCanada
  5. 5.Children’s Health Research InstituteLondonCanada
  6. 6.Department of Animal Care ServicesUniversity of British ColumbiaVancouverCanada
  7. 7.Division of Rheumatology, NYU Hospital for Joint DiseasesNew York University School of Medicine and NYU Langone Medical CenteNew YorkUSA

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