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2.3 Mitochondrial dysfunction To carry out their normal activity, chondrocytes need to be supplied with energy ( MMP , and decreases in OXPHOS ( 2.3.1 Reactive oxygen species production As well as generating ATP, mitochondria exercise a crucial function in other physiological processes within the cells, including the generation and modulation of ROS, the detection and regulation of hypoxic conditions by hypoxia-inducible factor-1 (HIF-1) , mitochondria-mediated apoptosis, and the accommodation of intracellular calcium ions ( mitochondrial DNA (mtDNA) damage and can also decrease the mtDNA repair capacity ( Figure 2 ) ( Figure 2 2.3.2 Mitochondria and the inflammatory response ROS enhances the inflammatory response in OA by stimulating signaling pathways, including NF-kB, MAPK, and PI3K/Akt ( TNFα, IL-1β , and IL-6 ) and MMPs , which damage the cartilage matrix ( Figure 3 ) ( MMPs (TIMPs) , which function as endogenous MMP inhibitors ( MMPs and TIMPs leads to increased extracellular matrix breakdown in OA chondrocytes
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