Articular cartilage repair using dedifferentiated articular chondrocytes and bone morphogenetic protein 4 in a rabbit model of articular cartilage defects

Abstract

To observe redifferentiation of dedifferentiated chondrocytes after transplantation into the joint, and to evaluate the ability of dedifferentiated chondrocytes transduced with adenovirus containing bone morphogenetic protein 4 (BMP-4) to redifferentiate in vitro and in vivo in a rabbit model of articular cartilage defects. Monolayer and pellet culture systems were used to evaluate the redifferentiation of dedifferentiated chondrocytes transduced with BMP-4. A rabbit model of partial-thickness articular cartilage defects was used to evaluate cartilage repair macroscopically and histologically, 6 and 12 weeks after transplantation with first-passage, fifth-passage, or transduced fifth-passage chondrocytes. Histologic grading of the repaired tissue was performed. Expression of BMP-4 and the ability of transplanted cells to recover a chondrocytic phenotype were also assessed. BMP-4--expressing dedifferentiated chondrocytes recovered a chondrocytic phenotype in vitro. After transplantation into the joint, some of the dedifferentiated chondrocytes in the defect sites could undergo redifferentiation and formed matrix that displayed positive toluidine blue staining for glycosaminoglycans. Histologic scores of the regenerative tissue revealed significantly better cartilage repair in rabbits transplanted with BMP-4--expressing cells than in the other treatment groups. Staining with toluidine blue revealed expression of BMP-4 in the cells and in the matrix surrounding the cells. Some dedifferentiated chondrocytes can redifferentiate after transplantation into the load-bearing joint. BMP-4 can be used to induce redifferentiation of dedifferentiated chondrocytes in vitro and in vivo, which could help enhance articular cartilage repair.