Regulation of the expression of the type-II collagen gene in periosteum-derived cells by three members of the transforming growth factor-beta superfamily

Although transforming growth factors-beta and bone morphogenetic proteins are both capable of inducing bone formation in vivo, the target cells of their osteoinductive actions may be different. To evaluate periosteal cells as potential targets of the actions of transforming growth factor-beta and bone morphogenetic protein, we investigated the ability of three members of the transforming growth factor-beta superfamily to modulate expression of the gene encoding the alpha 1(II) chain of type-II collagen in periosteum-derived cells in vitro. The results demonstrate that transforming growth factor-beta mRNA is expressed by periosteum-derived cells and that exogenous transforming growth factor-beta 1 acts to upregulate expression of the gene encoding collagen alpha 1(II). This effect was observed as early as 12 hours after administration of transforming growth factor-beta 1 but was not observed in response to bone morphogenetic proteins 3 or 4. No synergy was demonstrated between transforming growth factor-beta 1 and bone morphogenetic protein-3 in the ability to upregulate expression of the collagen alpha 1(II) gene. These results support the hypothesis that committed periosteal mesenchymal cells are cellular targets of the action of transforming growth factor-beta.