HES1 and osteoarthritis: Alteration of the osteoarthritis pathway due to RARγ agonist treatment was associated with the up-regulation of catabolic genes (ADAMTS5, HES1, and MMP13), inhibition of cartilage matrix anabolic genes (COL2A1, ACAN, and SOX9) and the up-regulation of death genes (CASP4) (Figure 2).