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National Institute of Environmental Health Sciences

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Publication Detail

Title: Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis.

Authors: Coleman, Mitchell C; Goetz, Jessica E; Brouillette, Marc J; Seol, Dongrim; Willey, Michael C; Petersen, Emily B; Anderson, Hope D; Hendrickson, Nathan R; Compton, Jocelyn; Khorsand, Behnoush; Morris, Angie S; Salem, Aliasger K; Fredericks, Douglas C; McKinley, Todd O; Martin, James A

Published In Sci Transl Med, (2018 02 07)

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.

PubMed ID: 29437147 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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