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Osteoarthritis—A mitochondrial malady
Articular cartilage—the smooth, avascular tissue that covers the bones in joints—can be damaged by traumatic injury, which can lead to osteoarthritis. In response to injury, chondrocytes ramp up mitochondrial activity, producing reactive oxygen species that can cause further tissue damage and cell death. Coleman and colleagues treated intra-articular fractures in a porcine model with an antioxidant or an inhibitor of the mitochondrial electron transport chain. Regulating mitochondrial metabolism prevented osteoarthritis. This work suggests that the mighty mitochondrion is a therapeutic target for posttraumatic osteoarthritis.
Abstract
We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.
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