REGULATION OF THE EXPRESSION OF THE TYPE-II COLLAGEN GENE IN PERIOSTEUM-DERIVED CELLS BY 3 MEMBERS OF THE TRANSFORMING GROWTH-FACTOR-BETA SUPERFAMILY

Although transforming growth factors-beta and bone morphogenetic prote ins are both capable of inducing bone formation in vivo, the target ce lls of their osteoinductive actions may be different. To evaluate peri osteal cells as potential targets of the actions of transforming growt h factor-beta and bone morphogenetic protein, we investigated the abil ity of three members of the transforming growth factor-beta superfamil y to modulate expression of the gene encoding the alpha 1(II) chain of type-II collagen in periosteum-derived cells in vitro. The results de monstrate that transforming growth factor-beta mRNA is expressed by pe riosteum-derived cells and that exogenous transforming growth factor-b eta 1 acts to upregulate expression of the gene encoding collagen alph a 1(II). This effect was observed as early as 12 hours after administr ation of transforming growth factor-beta 1 but was not observed in res ponse to bone morphogenetic proteins 3 or 4. No synergy was demonstrat ed between transforming growth factor-beta 1 and bone morphogenetic pr otein-3 in the ability to upregulate expression of the collagen alpha 1(II) gene. These results support the hypothesis that committed perios teal mesenchymal cells are cellular targets of the action of transform ing growth factor-beta.