Hypoxia and HIF-1α in chondrogenesis

摘要: In endochondral bone development chondrocytes undergo well-ordered and controlled phases of proliferation, hypertrophic differentiation, mineralization the surrounding matrix, death, blood vessel invasion, finally replacement cartilage with bone. The chondrocytic growth plate is a unique mesenchymal tissue, as it avascular but requires i.e. angiogenic switch, in order to be replaced by We have recently provided evidence that hypoxic during fetal development. Adaptation hypoxia critical event numerous pathological settings, such tumor progression survival tissues which flow has been suddenly interrupted. One hallmarks response activation transcription factor HIF-1alpha. von Hippel Lindau suppressor protein VHL component ubiquitin ligase promoting proteolysis By using genetic approach, we demonstrated essential role hypoxia/VHL/HIF-1alpha pathway Hypoxia-dependent up regulation HIF-1alpha transcriptional activity for chondrocyte, shapes inhibiting chondrocyte increasing matrix accumulation probably modulating cell size. findings overall highlight usefulness studying model address issues adaptation normal hypoxia, cells, switch. They also demonstrate crucial differentiation.