Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene
Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene
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DOI：
10.1038/sj.gt.3301608
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发表时间：
2002-01-01
期刊：
影响因子：
5.1
通讯作者：
McIlwraith, CW
中科院分区：
文献类型：
--
作者：
Frisbie, DD;Ghivizzani, SC;McIlwraith, CW
马和人类的骨关节炎是一个重要的社会和经济问题，需要继续研究和改进治疗方法。由于马具有与人类相似的天然骨关节炎，因此选择马作为研究基因转移作为骨关节炎临床治疗的潜在治疗方式的物种。使用建立的马骨关节炎模型，模拟临床骨关节炎，通过腺病毒介导的基因转移的马白细胞介素-1受体拮抗剂基因的关节内过表达的治疗效果进行了研究。马IL-IRa基因的体内递送导致白细胞介素-1受体拮抗剂的关节内表达升高约28天，导致疼痛和疾病活动性的临床参数的显著改善、关节软骨的保存以及对滑膜和关节软骨的组织学参数的有益作用。基于这些发现，白细胞介素-1受体拮抗剂的基因转移对于马患者是一种有吸引力的治疗方式，并且也为患有骨关节炎的人类患者提供了未来的希望。
Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intraarticular overexpression of the equine interieukin-1 receptor antagonist gene through adenoviral-mediated gene transfer were investigated. In vivo delivery of the equine IL-IRa gene led to elevated intra-articular expression of interleukin-1 receptor antagonist for approximately 28 days, resulting in significant improvement in clinical parameters of pain and disease activity, preservation of articular cartilage, and beneficial effects on the histologic parameters of synovial membrane and articular cartilage. Based on these findings, gene transfer of interieukin-1 receptor antagonist is an attractive treatment modality for the equine patient and also offers future promise for human patients with osteoarthritis.