Oxygen is thought to be an indispensable regulatory signal in tissue development and homeostasis, via its controlling of specific genetic programs. Hypoxia-inducible transcription factors (HIFs), which are regulated by oxygen tension, are central mediators of the homeostatic response that enables cells to survive and differentiate in low-oxygen conditions. In this Review, the authors summarize the current knowledge of HIF signalling in cartilage, bone and blood, and pay particular attention to the complex relationship between HIF and VEGF in these tissues based on data collected from animal models, which can also be relevant in diseases like cancer and ischemia.
- Christa Maes
- Geert Carmeliet
- Ernestina Schipani