Transforming growth factor β (TGFβ) family members are known for their important role in bone physiology. TGFβ1 and, to a smaller extent, bone morphogenetic protein 2 (BMP-2) have been reported to regulate the gene expression of different osteoblast markers in vitro. However, little is known about the molecular mechanisms involved in these actions. Here we report that BMP-2, like TGFβ1, up-regulated α1(I) collagen mRNA expression in ROS 17/2.8 osteoblastic cells. This was mediated through an increase in the transcriptional rate of the gene rather than through the stabilization of α1(I) collagen mRNA, and required new protein synthesis. In addition, TGFβ1- and BMP-2-induced increases in α1(I) collagen mRNA levels were both dependent on protein kinase C and protein tyrosine kinase activities. Furthermore, the mitogen-activated protein kinase (MAPK) [MAPK/extracellular signal-regulated protein kinase kinase 1/extracellular signal-regulated protein kinase (MEK-1/ERK)] pathway participated in the up-regulation of α1(I) collagen gene expression by TGFβ1 and BMP-2. In response to either TGFβ1 or BMP-2, the stimulation of α1(I) collagen mRNA levels was paralleled by an early increase in extracellular signal-regulated kinase protein activity. Moreover, the effects of both TGFβ1 and BMP-2 on α1(I) collagen gene expression were markedly decreased in transfected ROS 17/2.8 cells expressing a dominant-negative MEK-1. Our findings therefore show that TGFβ1 and BMP-2, which signal through discrete cell-surface receptors, are able to trigger analogous, if not identical, protein-phosphorylation-transducing cascades leading to comparable actions on the transcription of the α1(I) collagen gene in osteoblastic cells.
Protein kinase signalling pathways involved in the up-regulation of the rat α1(I) collagen gene by transforming growth factor β1 and bone morphogenetic protein 2 in osteoblastic cells