ROS generally increase during chondrogenesis, and ROS generated by NADPH oxidases 2 and 4 are necessary for chondrogenic differentiation of murine primary chondrocytes and the ATDC5 cell line [80]. Consistent with this, SOD3 levels were reduced upon chondrogenesis [75]; SOD3 is known to help reduce ROS in the extracellular matrix. Furthermore, ROS scavenging with NAC blocked chondrogenic differentiation [80]. Consistent with this, increasing ROS levels stimulated chondrocyte hypertrophy, and this effect was inhibited by NAC [81].