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

Zhibao Mi, Steven C. Ghivizzani, Eric Lechman, Joseph C. Glorioso, Christopher H Evans, Paul D. Robbins

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

To examine the effect of transforming growth factor (TGF)-beta1 on the regulation of cartilage synthesis and other articular pathologies, we used adenovirus-mediated intra-articular gene transfer of TGF-beta1 to both naïve and arthritic rabbit knee joints. Increasing doses of adenoviral vector expressing TGF-beta1 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-beta1 into the rabbit knee resulted in dose-dependent TGF-beta1 expression in the synovial fluid. Intra-articular TGF-beta1 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-beta1 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-beta1 may have anti-inflammatory properties, it is unable to stimulate repair of damaged cartilage, even stimulating cartilage degradation. Gene transfer of TGF-beta1 to the synovium is thus not suitable for treating intra-articular pathologies.

Original languageEnglish (US)
JournalArthritis Research & Therapy
Volume5
Issue number3
StatePublished - 2003
Externally publishedYes

Fingerprint

Transforming Growth Factor beta1
Adenoviridae
Transforming Growth Factor beta
Knee
Rabbits
Genes
Knee Joint
Joints
Arthritis
Cartilage
Pathology
Chondrogenesis
Intra-Articular Injections
Muscles
Patellar Ligament
Synovial Membrane
Synovial Fluid
Glycosaminoglycans
Luciferases
Edema

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Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees. / Mi, Zhibao; Ghivizzani, Steven C.; Lechman, Eric; Glorioso, Joseph C.; Evans, Christopher H; Robbins, Paul D.

In: Arthritis Research & Therapy, Vol. 5, No. 3, 2003.

Research output: Contribution to journalArticle

Mi, Zhibao ; Ghivizzani, Steven C. ; Lechman, Eric ; Glorioso, Joseph C. ; Evans, Christopher H ; Robbins, Paul D. / Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees. In: Arthritis Research & Therapy. 2003 ; Vol. 5, No. 3.
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