Reducing oxidative stress in mitochondria shortly after joint injury may prevent posttraumatic osteoarthritis (PTOA), according to a study published in Science Translational Journal. This discovery is compelling because young, active patients are more likely than older patients to experience these injuries, yet are not good candidates for joint replacement, given their young age.
Although some cartilage cells die upon impact in a joint injury, further cartilage cell death occurs in the 48 hours post-injury. Researchers sought to interrupt this cell destruction early in the process by “inhibiting mitochondrial metabolism with amobarbital, and boosting antioxidants in the chondrocytes with N-acetylcysteine (NAC).” Using a porcine model, which is well-suited to human-like surgical techniques and has anatomic similarities to the human ankle, researchers treated intra-articular fractures with an antioxidant or an inhibitor of the mitochondrial electron transport chain.
“We demonstrated that the PTOA that occurs in an ankle after a severe injury can be significantly blunted by inhibiting mitochondrial metabolism or adding key antioxidants immediately after injury,” says the study’s lead author, Mitchell Coleman, PhD, research assistant professor of orthopedics and rehabilitation at the University of Iowa Carver College of Medicine. “These treatments were only given twice, once right after injury and once a week later. No chronic therapy was used. Our data suggests that there might be a way to treat people acutely after they break their ankle to prevent PTOA.”
Coleman MC, Goetz JE, Brouillette MJ, el al. Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis. Science Transl Med. 2018;10(427): pii: eaan5372.