Skip to Main content Skip to Navigation
New interface
Journal articles

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

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.Proliferation of synoviocytes contributes to joint damage in rheumatoid arthritis. Here the authors show that targeting of these cells by a vector, consisting of a baculovirus conjugated to an adenovirus carrying the pro-apoptotic gene PUMA, has therapeutic efficacy in a rat arthritis model.
Document type :
Journal articles
Complete list of metadata

Cited literature [27 references]  Display  Hide  Download
Contributor : Marie-Gabrielle Chautard Connect in order to contact the contributor
Submitted on : Monday, May 25, 2020 - 11:04:55 AM
Last modification on : Wednesday, September 28, 2022 - 4:20:11 PM


2017_Saw-See_Nat_ Commun_1.pdf
Publisher files allowed on an open archive


Distributed under a Creative Commons Attribution 4.0 International License




Saw-See Hong, H. Marotte, G. Courbon, G. S. Firestein, Pierre Boulanger, et al.. PUMA gene delivery to synoviocytes reduces inflammation and degeneration of arthritic joints. Nature Communications, 2017, 8 (1), pp.146. ⟨10.1038/s41467-017-00142-1⟩. ⟨hal-02191892⟩



Record views


Files downloads