Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees

Arthritis Research & Therapy

Paul D Robbins²  Christopher H Evans¹  Joseph C Glorioso²  Eric Lechman²  Steven C Ghivizzani¹  Zhibao Mi² 

[1]Present address: Center for Molecular Orthopaedics, Harvard Medical School, Boston, Massacuhsetts, USA

[2]Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

关键词: transforming growth factor-β1;    rabbit model;    nitric oxide;    inflammatory;    cartilage degradation;    arthritis gene therapy;   

Others  :  1101391
DOI  :  10.1186/ar745

 received in 2002-03-18, accepted in 2003-02-04,  发布年份 2003

【 摘 要 】

To examine the effect of transforming growth factor (TGF)-β1 on the regulation of cartilage synthesis and other articular pathologies, we used adenovirus-mediated intra-articular gene transfer of TGF-β1 to both naïve and arthritic rabbit knee joints. Increasing doses of adenoviral vector expressing TGF-β1 were injected into normal and antigen-induced arthritis rabbit knee joints through the patellar tendon, with the same doses of an adenoviral vector expressing luciferase injected into the contralateral knees as the control. Intra-articular injection of adenoviral vector expressing TGF-β1 into the rabbit knee resulted in dose-dependent TGF-β1 expression in the synovial fluid. Intra-articular TGF-β1 expression in both naïve and arthritic rabbit knee joints resulted in significant pathological changes in the rabbit knee as well as in adjacent muscle tissue. The observed changes induced by elevated TGF-β1 included inhibition of white blood cell infiltration, stimulation of glycosaminoglycan release and nitric oxide production, and induction of fibrogenesis and muscle edema. In addition, induction of chondrogenesis within the synovial lining was observed. These results suggest that even though TGF-β1 may have anti-inflammatory properties, it is unable to stimulate repair of damaged cartilage, even stimulating cartilage degradation. Gene transfer of TGF-β1 to the synovium is thus not suitable for treating intra-articular pathologies.

【 授权许可】

   
2003 Mi et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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