Signaling pathways regulating the specification and differentiation of the osteoblast lineage

Tissue engineering is an approach to the regeneration of tissues that uses a combination of cell sources, signaling factors and scaffolds. Among these three components, signaling factors for bone regeneration have not yet been established, and it is necessary to better understand osteoblast progenitors as a target cells. Several lines of evidence have revealed that, during bone formation, mesenchymal cells are specified and differentiate into osteoblasts through several stages of precursors. The osteoblast lineage is defined by the expression of stage-specific transcription factors. The specification and differentiation are organized by a variety of signaling pathways including hedgehog (Hh), Wnt, Notch, bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFβ). In this review we integrate the known functions of these signaling pathways and discuss future tasks to gain a better understanding of the signaling network in osteogenesis for tissue engineering.