Loss of Hif1α in chondrocytes accelerates OA progression and induces increased MMP13 expression in mice.49 Transgenic mice overexpressing HIF2α show spontaneous cartilage destruction.50 Our group also found that upregulated Hif2α led to accelerated development of age-associated and surgically induced OA in Vhl-deficient mice.51 However, only a few studies have explored the in vivo role of HIFα in regulating DDD pathogenesis at the adult stage.19 The findings of this study showed aberrant HIF1α signaling in EP and AF tissues of degenerated human and mouse discs. The gene discussed is EPAS1; the disease is Dowling-Degos disease 1.