Coleman, Mitchell C.Goetz, Jessica E.Brouillette, Marc J.Seol, DongrimWilley, Michael C.Peterson, Emily B.Anderson, Hope D.Hendrickson, Nathan R.Compton, Jocelyn T.Khorsand, BehnoushMorris, Angie S.Salem, Aliasger K.Fredericks, Douglas C.McKinley, Todd O.Martin, James A.2019-05-082019-05-082018-02-07Coleman, M. C., Goetz, J. E., Brouillette, M. J., Seol, D., Willey, M. C., Petersen, E. B., … Martin, J. A. (2018). Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis. Science translational medicine, 10(427), eaan5372. doi:10.1126/scitranslmed.aan5372https://hdl.handle.net/1805/19193We 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.en-USPublisher PolicyArticular chondrocyte mitochondriaSevere traumatic injuryPosttraumatic osteoarthritis (PTOA)Intra-articular fracturesOxidative stressArticle