Signals that determine the fate of osteoblastic cells.

Signals that determine skeletal cell fate, function and apoptosis are critical to normal bone remodeling. Skeletal cells synthesize growth factors; some regulate cell replication, others regulate osteoblastic differentiation. Bone morphogenetic proteins (BMP) and Wnts induce the differentiation of mesenchymal cells toward mature osteoblasts. The action of BMPs is regulated by extracellular antagonists. These often act by binding to BMPs and preventing their binding to cell surface receptors. Wnt is essential for osteoblastogenesis, and mutations of Wnt co-receptors are associated with changes in bone mass. Wnt activity, like BMPs, is regulated by extracellular and intracellular antagonists. Notch, a family of transmembrane receptors, opposes Wnt signaling and inhibits osteoblastic differentiation. BMP, Wnt and Notch play a central role in osteoblastic cell fate.