BMP Signaling in Osteogenesis, Bone Remodeling and Repair

Bone morphogenetic proteins (BMPs) have unique properties as inducers of differentiation of chondrocytes and osteoblasts from pluripotent mesenchymalprogenitors, and also support terminal osteoblast differentiation and modulate osteoclast fate. These properties constitute only one, but central, aspect of the functions BMPs have during animal development and in adult animal homeostasis. Emphasis is given to the established signal transduction mechanisms initiated by BMPs during osteogenesis, which include the intracellular Smad effectors and alternative proteins. The complexity of differentiation processes that BMPs seem to govern during bone formation draw our attention to the mechanisms that attribute precision in the signal transduction pathways. These involve extra cellular regulators of BMP ligands, intracellular ubiquitin-mediated processes and nuclear, transcriptional mechanisms. Finally, certain pathophysiological links of BMP signaling to bone disease and processes critically involved during trauma are discussed, thus addressing recent developments in bone remodeling and repair. [PUBLICATION ABSTRACT]