Lack of HIF-2alpha in limb bud mesenchyme causes a modest and transient delay of endochondral bone development.

摘要

Two papers recently published in Nature Medicine provide evidence that hypoxia-inducible factor-2alpha (HIF-2alpha) is crucial for articular surface homeostasis through mechanisms that involve, at least in part, regulation of genes such as Coll10a1 (encoding the alphal chain of type X collagen, CollOAl), Mmpl3 (encoding matrix metallo-proteinase-13, MMP-13) and Vegfa (encoding vascular endothelial growth factor-A, VEGF). Interestingly, Saito et al. also report a mild delay of chondrocyte hypertrophy in fetal growth plates of mice heterozygous for genetic knockout of HIF-2alpha (encoded by Epasl). The key implication of this finding is that homozygous loss of HIF-2a would markedly delay chondrocyte hypertrophy and replacement of cartilage by bone. However, as shown below, we found that this was not the case.