BMP Signaling Is Required for RUNX2-Dependent Induction of the Osteoblast Phenotype

Abstract

C3H10T1/2 cells constitutively synthesize BMP2 and 4 mRNA and protein, and this BMP activity is sufficient to activate basal levels of SMAD phosphorylation. Inhibition of BMP signaling was shown to disrupt the ability of RUNX2 to stimulate osteoblast differentiation and transactivate an osteocalcin gene promoter-luciferase reporter in C3H10T1/2 cells. BMP blocking antibodies also inhibited RUNX2-dependent osteoblast differentiation in primary cultures of murine marrow stromal cells. Conversely, RUNX2 expression synergistically stimulated BMP2 signaling in C3H10T1/2 cells. However, RUNX2 did not increase the ability of this BMP to activate SMAD, ERK, p38, and JNK pathways. This study shows that autocrine BMP production is necessary for the RUNX2 transcription factor to be active and that BMPs and RUNX2 cooperatively interact to stimulate osteoblast gene expression.