OSF2 CBFA1 - A TRANSCRIPTIONAL ACTIVATOR OF OSTEOBLAST DIFFERENTIATION/

The osteoblast is the bone-forming cell. The molecular basis of osteob last-specific gene expression and differentiation is unknown. We previ ously identified an osteoblast-specific cis-acting element, termed OSE 2, in the Osteocalcin promoter. We have now cloned the cDNA encoding O sf2/Cbfa1, the protein that binds to OSE2. Osf2/Cbfa1 expression is in itiated in the mesenchymal condensations of the developing skeleton, i s strictly restricted to cells of the osteoblast lineage thereafter, a nd is regulated by BMP7 and vitamin D-3. Osf2/Cbfa1 binds to and regul ates the expression of multiple genes expressed in osteoblasts. Finall y, forced expression of Osf2/Cbfa1 in nonosteoblastic cells induces th e expression of the principal osteoblast-specific genes. this study id entifies Osf2/Cbfa1 as an osteoblast-specific transcription factor and as a regulator of osteoblast differentiation.