Molecular mechanisms of osteoblast-specific transcription factor Osterix effect on bone formation.

Abstract

Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts. Osteoblast commitment and differentiation are controlled through a multistep molecular pathway regulated by different transcription factors and signaling proteins, including Indian hedgehog, Runx2, Osterix (Osx), and Wnt pathway. Osx is an osteoblast-specific transcription factor required for bone formation. Osx was first discovered as a bone morphogenetic protein-2 inducible gene in mesenchymal stem cells. Osx knock-out mice lack bone completely, and cartilage is normal. This opens a new window to the whole field of how bone forms. The discovery that Osx inhibits Wnt pathway highlights the potential for novel feedback control mechanisms involved in bone formation. Several downstream targets of Osx during bone formation have been identified, including Satb2, vitamin D receptor and vascular endothelial growth factor as well as Dkk1 and Sost. The delineation of the cascade of events leading to bone formation should provide a molecular basis for the development of new and specific anabolic therapeutic agents for bone deficit conditions, such as osteoporosis and osteonecrosis. This review summarizes the recent advances in understanding the molecular mechanisms of Osx effect on bone formation. Studies since the Osx discovery have provided convincing evidences to demonstrate that Osx is the master gene that controls osteoblast lineage commitment and the subsequent osteoblast differentiation and proliferation.