Regulation of cartilage destruction using tissue-specific expression system

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The present study can be summarized into four categories ; analysis of genes responsible for cartilage damage, analysis of tissue-specific element of Col11a2 gene, prevention of cartilage damage and its repair. Firstly, we demonstrated that aggrecan gene VNTR in the core protein coding region and VDR allele are associated with the degeneration of intervertebral disc cartilage. We then identified cartilage tissue specific cis-element of Col11a2 and used this element for the tissue specific expression of marker gene after in vivo gene transfer. To further improve such gene transfection efficiency we developed a new superfine-pointed 7-needle electrodes for in vivo electroporetion. Bearing these background results, we then prepared engineered mesenchymal cells from the bone marrow (MSCs) by transfecting cartilage-derived morphogenetic protein 1 (CDMP1). The cells were used for transplantation into full-thickness articular cartilage defect in rabbit knee joint and the specimens were evaluated histologically. During in vivo repair of articular cartilage defect, cartilage regeneration was significantly enhanced with transplantation of CDMP1-transfected MSCs. The defect was filled with hyaline cartilage and the deeper zone was remodeled to subchondral bone with time. The histological score of CDMP1-transfected MSCs group was better than those of control MSCs group and empty control. The results demonstrated that CDMP1-transfected MSCs maintained cell growth activity, showed enhanced progression toward chondrogenic lineage and improved the in vivo cartilage repair.