Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage

Christine M Latham, Peyton J Balawender, Nicholas T Thomas, Alexander R Keeble, Camille R Brightwell, Ahmed Ismaeel, Yuan Wen, Jean L Fry, Patrick G Sullivan, Darren L Johnson, Brian Noehren, Allison M Owen, Christopher S Fry

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD+/-). MnSOD+/- mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalFree Radical Biology and Medicine
Volume26
Issue number212
DOIs
StateE-pub ahead of print - Dec 26 2023

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