Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Article numbereaan5372
JournalScience Translational Medicine
Volume10
Issue number427
DOIs
StatePublished - Feb 7 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 The Authors.

Fingerprint

Dive into the research topics of 'Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis'. Together they form a unique fingerprint.

Cite this