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PUMA gene delivery to synoviocytes reduces inflammation and degeneration of arthritic joints

Author

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  • Saw-See Hong

    (University of Lyon
    University of Lyon
    INSERM, 101 rue de Tolbiac)

  • Hubert Marotte

    (University Jean Monnet University of Lyon)

  • Guillaume Courbon

    (University Jean Monnet University of Lyon)

  • Gary S. Firestein

    (University of California at San Diego)

  • Pierre Boulanger

    (University of Lyon
    University of Lyon)

  • Pierre Miossec

    (University of Lyon
    Hôpital Edouard Herriot, University of Lyon)

Abstract

In rheumatoid arthritis (RA), the proliferation of fibroblast-like synoviocytes (FLS) is the cause of chronic inflammation in joints and of joint damage. Delivery of the pro-apoptotic gene PUMA to FLS via human adenovirus type 5 (HAdV5) vectors has been tested as a therapeutic approach, but efficiency is hampered by low transduction, as FLS do not express HAdV5 receptors on the cell surface. Here we show that efficient transduction of PUMA in FLS can be achieved by conjugating HAdV5 to a baculovirus, which binds to the cell surface via the envelope glycoprotein Gp64. Intra-articular injection in an adjuvant-induced rat model of RA induces apoptosis of FLS, leading to significant decrease in joint inflammation, joint damage, and bone loss with improvement in joint function and mobility. Our results demonstrate the therapeutic potential of PUMA gene therapy as a local treatment in various forms of arthritis in which abnormal FLS proliferation is implicated.

Suggested Citation

  • Saw-See Hong & Hubert Marotte & Guillaume Courbon & Gary S. Firestein & Pierre Boulanger & Pierre Miossec, 2017. "PUMA gene delivery to synoviocytes reduces inflammation and degeneration of arthritic joints," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00142-1
    DOI: 10.1038/s41467-017-00142-1
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    Cited by:

    1. Haobo Han & Jiakai Xing & Wenqi Chen & Jiaxin Jia & Quanshun Li, 2023. "Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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