More marrow and weaker bones in mice with excess Cbfa1 (right).
Many growth factors that promote the formation of bone-forming cells called osteoblasts are thought to act through a transcription factor called core binding factor α1 (Cbfa1). Mice lacking Cbfa1 fail to form any mature osteoblasts or bones, and experiments with a dominant negative form of Cbfa1 have suggested that the protein is important in regulating osteoblast functions such as matrix formation and mineralization.
Now, Liu et al. (page 157) find that mice overexpressing Cbfa1 in their osteoblasts have weak bones and multiple fractures within a few weeks after birth. Immature osteoblasts accumulate, suggesting that the excess Cbfa1 inhibits a late stage of osteoblast maturation. Thus, Cbfa1 is essential early in maturation but must then be downregulated to allow final maturation. ▪