In recent years, it has been proposed that oxygen is not only an indispensable metabolic substrate, but also a regulatory signal, and that gradients of oxygenation turn on a specific genetic program. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor hypoxia-inducible factor 1alpha (Hif-1alpha). The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out-in gradient of oxygenation. Hif-1alpha is required for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in an hypoxic environment. Preliminary evidence suggests that regulation of posttranslational modifications of collagens could be an important component of this adaptive response.