Molecular mechanisms of osteoblast-specific transcription factor Osterix effect on bone formation.
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.
University of Texas Southwestern Medical Center, Dallas, TX 75219, USA. Chi5.Zhang@utsouthwestern.edu
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D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*; D060449:Wnt Signaling Pathway
D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors