The role of TGF-β and BMP-7 in regenerating bone and soft tissues

Abstract

The involvement of transforming growth factor-β (TGF-β) in the formation and repair of connective tissues and the related bone morphogenic proteins (BMPs) in bone induction has been well established. However, the ability of TGF-β to promote rapid repair results in scarring whereas the effect of BMPs on soft connective tissues is largely unknown. In order to evaluate the potential of TGF-β and BMPs, alone and in combination, in regenerating hard and soft connective tissues, such as those found in the periodontium, we have been studying the influence of these cytokines on fibroblast and bone cell metabolism. In earlier studies we have shown that TGF-β1 stimulates matrix formation through increased transcription of matrix protein genes while suppressing genes coding for matrix degrading enzymes in both fibroblasts and bone cells. However, TGF-β1 alone suppresses the expression of alkaline phosphatase and the formation of mineralized tissue in vitro, whereas BMP-7 stimulates bone matrix protein expression and alkaline phosphatase in association with bone formation. Recent studies also indicate that BMP-7 stimulates the clonal expansion of pre-osteoblasts, thereby increasing the number of bone-forming cells. In contrast to osteogenic cells, however, fibroblasts appear refractory towards BMP-7. Thus, the effects of TGF-β and BMP are clearly discrete and are dependent upon the responding cell populations. If used in combination these cytokines could promote the formation of both hard and soft connective tissues.