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Updated: Aug 7, 2026
In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
Published on: May 6, 2018
Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees
Zhibao Mi1, Steven C Ghivizzani, Eric Lechman
1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
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.
Insights
Transforming growth factor (TGF)-beta1 gene transfer to rabbit knees did not repair cartilage. Elevated TGF-beta1 worsened joint pathology and cartilage degradation, indicating it
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Orthopedics
Background:
- Transforming growth factor (TGF)-beta1 plays a role in cartilage homeostasis.
- Its therapeutic potential for articular pathologies remains unclear.
- Investigating TGF-beta1's effects on cartilage synthesis and joint disease is crucial.
Purpose of the Study:
- To evaluate the impact of intra-articular TGF-beta1 gene transfer on cartilage synthesis.
- To assess TGF-beta1's effects on naive and arthritic rabbit knee joints.
- To determine the suitability of TGF-beta1 gene therapy for intra-articular pathologies.
Main Methods:
- Adenovirus-mediated intra-articular gene transfer of TGF-beta1 in rabbit knees.
- Use of luciferase as a control in contralateral knees.
- Dose-dependent administration into naive and antigen-induced arthritis models.
Main Results:
- Intra-articular TGF-beta1 increased in synovial fluid dose-dependently.
- Pathological changes observed in knee joints and surrounding muscle.
- Inhibition of white blood cell infiltration, stimulated glycosaminoglycan and nitric oxide release, fibrogenesis, muscle edema, and synovial chondrogenesis.
Conclusions:
- TGF-beta1 exhibits anti-inflammatory properties but does not stimulate cartilage repair.
- Elevated TGF-beta1 leads to cartilage degradation and joint pathology.
- Intra-articular TGF-beta1 gene transfer is unsuitable for treating joint diseases.
