Application of IL-4 Transgene Expression in a Chondrocyte-Based 3D Modell of Inflammatory Arthritis

Osteoarthritis (OA) is the most common form of arthritis with unknown pathology. However, it is believed to be due to consequence of mechanical and biological events that destabilize the normal coupling of degradation and synthesis within articular joint tissues. Although this disease has a history of many centuries, still a complete cure is not possible leaving joint replacement as the only alternative in chronic patients. Gene therapy has been proposed as an alternative to traditional medical treatment. Developing gene-based therapy for OA and rheumatoid arthritis (RA) in both human and veterinary patients represents an exciting challenge. The detailed understanding of the disease pathogenesis has enabled the introduction and characterization of therapeutic gene. In this case IL-4 was used to test for its anti-inflammatory properties in an in vitro model of inflammatory arthritis based on chondrocytes. The results from this study provided a solid foundation to validate constructs with cytokine responsive “intelligent” promoter, which was developed in this laboratory alongside experimental work for this thesis. Thus, using the cell culture systems described here it was shown that only in the presence of inflammation, the expression of IL-4 is driven in a sophisticated and fine-tuned manner. Therefore, combining the cell culture systems with the application of regulatable delivery of transgenes (IL-4 or other promising candidate genes) will facilitate further development and testing of novel gene therapy strategies against OA (and RA).