[Tissue regeneration induced by a transgene for bone morphogenetic protein-12 (BMP-12) in a bone defect]

BMP-12, other than BMP-2, 4, and 7, is known to induce the formation of tendon/ligament-like tissues. However, the role of the protein in the process of bone or cartilage healing has not been adequately examined. The purpose of the present study was to examine if a plasmid vector encoding BMP-12 would induce tendon/ ligament formation in a rat bone defect model. A lyophilized atelocollagen pellet with 100 microg of a plasmid vector encoding BMP-12 or BMP-2 was implanted in a bone defect of a rat femoral metaphysis. The samples were retrieved at 2, 4 and 8 weeks post-operation and subjected to histology and real-time PCR analysis. BMP-12 transgene indicated prominent fibrogenesis at 2 weeks. Consequently, the tissue was substituted by bone at 8 weeks. The gene expression of collagen type III was up-regulated by BMP-12 gene transfer after 2 weeks, followed by an increase of elastin and Six1 genes after 4 weeks. These genes, which are intimately related to tendon/ligament formation, decreased in expression at 8 weeks in preparation for osteogenesis afterward. On the other hand, the BMP-2 transgene quickly induced the synthesis of bone-related genes such as collagen type I and ALP. It is concluded that BMP-12 can initiate the development of tendon/ligament-like tissue in a rat bone defect at early healing stages. Maintaining such generation of tissue on bone could be useful for modifying periodontal tissue engineering.