Gene therapy for osteochondral defect

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1. To determine the therapeutic effect of FGF-2 mediated adenovirus vector on the osteochondral injury of the knee joints, AdCAsFGF-2 was administrated to the male Wister rats intravenously, in which knee joint osteochondral defect model was made by drilling with a surge-airtome. It was observed that cartilage repair was seen in the knee joints of rats with which were administrated AdCAsFGF-2 compared with rats injected with AxCAEGFP, control virus. Although there was the problem to induce the inflammation by AdCAsFGF-2, it seemed that local administration with vecotrs could be a therapeutic method for osteochondral injury.2. To examine the effect of IL-4 on matrix synthesis in chondrocytes under excessive mechanical stress in vitro. Mechanical stress for 16 hours significantly decreased levels of mRNA for both AGG and CII (p <0.01), but rat IL-4 at doses of 1 or 10 ng/ml recovered these levels (p <0.05). These findings suggested that IL-4 might prevent articular cartilage from damage caused by mechanical stress and therefore could be a useful therapeutic agent for treatment of arthritic disorders.3. Fibronectin is one of the major extracellular matrix components in synovium, and it plays a central role in cell-cell and cell-matrix interactions through ligation of cell surface integrins. In the present study, a 15 amino acid peptide derived from the carboxy-terminal 33-kD cell and heparin-binding domain of fibronectin (FN-C/H-II) suppressed established arthritis in mice, associated with reduced infiltration of inflammatory cells into the joint.