Amelioration of experimental arthritis by a telomerase-dependent conditionally replicating adenovirus that targets synovial fibroblasts

Shih Yao Chen, Ai Li Shiau, Gia Shing Shieh, Chih Hau Su, Che Hsin Lee, Hwei Ling Lee, Chrong Reen Wang, Chao Liang Wu

研究成果: Article同行評審

8 引文 斯高帕斯(Scopus)


Objective. Synovial fibroblasts (SFs) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It has been documented that the phenotype of rheumatoid synovium is similar, in many respects, to that of an aggressive tumor. In this study, a novel, genetically engineered adenovirus was designed to lyse SFs that exhibit high telomerase activity and p53 mutations, and its effects as a novel therapeutic strategy were assessed in an experimental arthritis model. Methods. An E1B-55-kd-deleted adenovirus driven by the human telomerase reverse transcriptase promoter was constructed (designated Ad.GS1). Cytolysis of SFs and productive replication of Ad.GS1 in the SFs of rats with collagen-induced arthritis (CIA), as well as the SFs of patients with RA (RASFs), were assessed in vitro and in vivo. Treatment responses, as well as the presence of disease-related cytokines and enzymes in the ankle joints, were determined in the murine model. Results. Ad.GS1 replicated in and induced cytolysis of human RASFs and SFs from arthritic rats, but spared normal fibroblasts. Bioluminescence imaging in vivo also demonstrated replication of Ad.GS1 in arthritic rat joints, but not in normal rat joints. Intraarticular administration of Ad.GS1 significantly reduced the ankle circumference, articular index scores, radiographic scores, and histologic scores and decreased the production of interleukin-1β, matrix metalloproteinase 9, and prolyl 4-hydroxylase in rats with CIA compared with their control counterparts. Conclusion. This study is the first to demonstrate the amelioration of arthritic symptoms by a novel, telomerase-dependent adenovirus in the rat CIA model, an experimental model that resembles human RA. In addition, the results suggest that because of its ability to induce cytolysis of SFs, this virus may be further explored as a therapeutic agent in patients with RA.

頁(從 - 到)3290-3302
期刊Arthritis and Rheumatism
出版狀態Published - 2009 11月

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 風濕病
  • 免疫學
  • 藥學(醫學)


深入研究「Amelioration of experimental arthritis by a telomerase-dependent conditionally replicating adenovirus that targets synovial fibroblasts」主題。共同形成了獨特的指紋。