SOD2 orchestrates redox homeostasis in intervertebral discs: A novel insight into oxidative stress-mediated degeneration and therapeutic potential

• DOI: 10.1016/j.redox.2024.103091
• Publication Date: 2024-02-19T17:24:53Z
• Authors: Shota Tamagawa; Daisuke Sakai; Hidetoshi Nojiri; Yoshihiko Nakamura; Takayuki Warita; Erika Matsushita; Jordy Schol; Hazuki Soma; Shota Ogasawara; Daiki Munesada; Masato Koike; Takahiko Shimizu; Masato Sato; Muneaki Ishijima; Masahiko Watanabe
• Keywords: SOD2

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute IVD degeneration, the underlying mechanisms remain undetermined. This study aimed unravel role of superoxide dismutase 2 (SOD2) in pathogenesis and target limit SOD2 demonstrated dynamic regulation surgically excised human tissues, initial upregulation moderate degeneration downregulation severely degenerated IVDs. Through comprehensive set vitro vivo experiments, we found suggestive association between excessive mitochondrial superoxide, cellular senescence, matrix degradation mouse cells. We confirmed that aging mechanical stress, established triggers for escalated levels models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related stress-induced mice, could be attenuated by β-nicotinamide mononucleotide treatment. These revelations underscore central redox balance unveil potential therapeutic avenues, making promising targets effective LBP interventions.