Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low-Grade Inflammation in Osteoarthritis

Figure 2

(a) Sources of ROS in the chondrocyte. The major sources of ROS are the mitochondria, during the OXPHOS. In addition, ROS can be generated at the level of the endoplasmic reticulum (ER), in condition of ER stress. An additional source is represented by the peroxisome, during the β-oxidation of long chain-fatty acids (LCFA), particularly under conditions of excess LCFA load. Various enzymes, with different cell location may also generate ROS. (b) Production of ROS and RNS involved in OA pathogenesis, and major detoxifying enzymes. The first generated ROS is the superoxide (O₂⁻) that is either rapidly transformed into hydrogen peroxide (H₂O₂) by the enzymes of the superoxide dismutase (SOD) family or can act as a precursor for peroxynitrite (ONOO⁻) formation when joined to nitric oxide (NO), produced by the enzymes of the nitric oxide synthase (NOS) family. Because of unpaired electrons, free radicals are very reactive and can damage cell components. In chondrocytes, iron Fe²⁺ and H₂O₂ release hydroxyl radicals (OH⁻) that react with unsaturated fatty acids of membrane lipids, thus forming lipid radicals (RO^•, ROO^•). ROS are neutralized by scavenging systems, namely, SOD, catalase, glutathione peroxidase, glutathione reductase, and reduced glutathione.

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