Figure 1: Schematic diagram showing the key role of ROS in age-related chondrocyte changes. Excessive levels of ROS inhibited matrix synthesis (aggrecan, type II collagen) by suppressing the IRS-1-PI-3 kinase-Akt signaling pathway or by activating the ERK MAPK signaling pathway. Sustained activation of ERK can induce cell senescence. In addition, extracellular ROS could also contribute to the inhibition of the Akt pathway through oxidized low-density lipoprotein (LDL). The binding of oxidized LDL to cell surface receptor LOX-1 was found to induce chondrocyte senescence (blue arrow).