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

Free Radic Biol Med. 2024 Feb 20:212:191-198. doi: 10.1016/j.freeradbiomed.2023.12.037. Epub 2023 Dec 26.

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.

Keywords: Anterior cruciate ligament; Knee injury; Mitochondria; Quadriceps; Reactive oxygen species; Skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anterior Cruciate Ligament Injuries* / complications
  • Anterior Cruciate Ligament Injuries* / genetics
  • Anterior Cruciate Ligament Injuries* / surgery
  • Antioxidants / metabolism
  • Humans
  • Knee Injuries* / complications
  • Knee Injuries* / surgery
  • Mice
  • Muscle Weakness / complications
  • Muscle Weakness / genetics
  • Muscular Atrophy / genetics
  • Muscular Atrophy / prevention & control
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Superoxide Dismutase