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-1α 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.