ACAN and osteoarthritis: Furthermore, Yang et al. found that NAMPT exerts its catabolic function by downregulating aggrecan and upregulating MMP3 and MMP13, which is a key characteristic of osteoarthritis pathogenesis and a direct target of Hypoxia‐inducible factor 2‐alpha (HIF‐2α) in articular chondrocytes and osteoarthritis cartilage18.