Cartilage oxidation is a central feature of OA pathology, but the age-related mechanisms underlying its etiopathogenesis are poorly understood. We recently discovered that aging impairs the specific activity of the mitochondrial antioxidant SOD2 due to a decline in the mitochondrial deacetylase SIRT3. This work implicates mitochondrial acetylation as a critical mediator of chondrocyte redox regulation and cartilage matrix homeostasis. We are using mouse genetic models to conditionally delete or over-express SIRT3 in cartilage. These studies will allow us to determine in vivo how SIRT3 regulates age-dependent declines in cartilage stress resilience and metabolic dysfunction. An additional goal is to identify the cartilage proteolytic enzymes that are activated under these conditions of increased mitochondrial acetylation and inflammation.
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