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Suppression of early experimental osteoarthritis by gene transfer of interleukin‐1 receptor antagonist and interleukin‐10
Author(s) -
Zhang Xiaoling,
Mao Zebing,
Yu Changlong
Publication year - 2004
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/j.orthres.2003.12.007
Subject(s) - interleukin 1 receptor antagonist , cartilage , osteoarthritis , interleukin 1 receptor , receptor antagonist , interleukin , gene expression , complementary dna , arthritis , gene delivery , genetic enhancement , gene , synovial membrane , immunology , medicine , transfection , cancer research , microbiology and biotechnology , receptor , biology , antagonist , pathology , cytokine , anatomy , genetics , alternative medicine
Gene therapy offers a radically different approach to the treatment of arthritis. We demonstrated that cDNA coding for human interleukin‐1 receptor‐antagonist protein (IL‐1Ra) and cDNA coding for human interleukin‐10 (IL‐10) can be delivered, by ex vivo techniques, to the synovial lining of joints, intra‐articular expression of gene significantly reduced cartilage matrix degradation and cartilage breakdown. To achieve this, lapine synoviocytes were first transduced in culture by retroviral infection. The genetically modified synoviocytes were then transplanted by intra‐articular injection into the knee joints of OA rabbits, assay of joint lavages confirmed that the gene expression was not lost 14 days after transfer. Knees receiving the IL‐1Ra gene had significantly reduced cartilage breakdown. Delivery of the IL‐10 gene was less effective, having only a moderate effect on cartilage breakdown. When both genes were injected together, there was a greater inhibition of cartilage breakdown, suggesting that simultaneous gene delivery may be necessary to treat OA by targeting the activities of multiple inflammatory effectors. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.