BONE MORPHOGENETIC PROTEINS (BMP-2 AND BMP-3) INDUCE THE LATE PHASE EXPRESSION OF THE PROTOONCOGENE C-FOS IN MURINE OSTEOBLASTIC MC3T3-E1 CELLS

Here we report that bone morphogenetic proteins 2 and 3 (BMP-2 and BMP-3) induced marked expression of c-fos mRNA in a biphasic manner, i.e. the late phase (48 to 60 h) as well as the immediate-early phase (0.5 h), in murine osteoblastic MC3T3-E1 cells in vitro. The BMP-induced late phase c-fos gene expression was temporally associated with the onset of marked expression of the genes for osteocalcin and alkaline phosphatase, differentiation markers of mature osteoblasts. In contrast, none of TGF-beta1, 10% FBS, IGF-I and IGF-II, which induced only the immediate-early c-fos mRNA expression, stimulated the expression of osteocalcin and alkaline phosphatase genes. These data suggest that in osteoblasts BMP-2 and BMP-3 induce the late phase expression of c-fos, which may play a role in transcriptional activation of the genes involved in differentiation of osteoblasts.