Hypoxia, HIFs and bone development

Oxygen is not only an obviously important substrate, but it is also a regulatory signal that controls expression of a specific genetic program. Crucial mediator of the adaptive response of cells to hypoxia is the family of Hypoxia-inducible Transcription Factors (HIFs). The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out-in gradient of oxygenation. HIF-1 alpha is necessary for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in a hypoxic environment. Moreover. HIFs are also essential in osteogenesis and joint development. This brief Perspective summarizes the critical role of HIFs in endochondral bone development. (C) 2010 Elsevier Inc. All rights reserved.