Browsing by Subject "Posttraumatic osteoarthritis (PTOA)"

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    Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis
    (American Association for the Advancement of Science, 2018-02-07) Coleman, Mitchell C.; Goetz, Jessica E.; Brouillette, Marc J.; Seol, Dongrim; Willey, Michael C.; Peterson, Emily B.; Anderson, Hope D.; Hendrickson, Nathan R.; Compton, Jocelyn T.; Khorsand, Behnoush; Morris, Angie S.; Salem, Aliasger K.; Fredericks, Douglas C.; McKinley, Todd O.; Martin, James A.; Orthopaedic Surgery, School of Medicine
    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.