Potential Involvement of Oxidative Stress in Ligamentum Flavum Hypertrophy

Kei Ito, Hideki Kise, Satoshi Suzuki, Sota Nagai, Kurenai Hachiya, Hiroki Takeda, Soya Kawabata, Daiki Ikeda, Keiyo Takubo, Shinjiro Kaneko, Nobuyuki Fujita

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Oxidative stress (OS) results in many disorders, of which degenerative musculoskeletal conditions are no exception. However, the interaction between OS and ligamentum flavum (LF) hypertrophy in lumbar spinal canal stenosis is not clearly understood. The first research question was whether OS was involved in LF hypertrophy, and the second was whether the antioxidant N-acetylcysteine (NAC) was effective on LF hypertrophy. In total, 47 LF samples were collected from patients with lumbar spinal disorders. The cross-sectional area of LF was measured on axial magnetic resonance imaging. Immunohistochemistry of 8-OHdG and TNF-α were conducted on human LF samples. A positive association was found between 8-OHdG or TNF-α expression and cross-sectional area of LF. Flow cytometry analysis showed that H2O2, buthionine sulfoximine, and TNF-α treatment significantly increased intracellular reactive oxygen species in primary LF cells. NAC inhibited the induction of LF hypertrophy markers by OS or TNF in a real-time reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Western blotting analysis indicated that p38, Erk, and p65 phosphorylation were involved in intracellular OS signaling in LF cells. In conclusion, our results indicated that OS could be a therapeutic target for LF hypertrophy. Although this study included no in vivo studies to examine the longitudinal efficacy of NAC on LF hypertrophy, NAC may have potential as a therapeutic agent against lumbar spinal canal stenosis.

Original languageEnglish
Article number808
JournalJournal of Clinical Medicine
Issue number3
Publication statusPublished - 2023 Feb


  • N-acetylcysteine
  • ligamentum flavum hypertrophy
  • lumbar spinal canal stenosis
  • oxidative stress
  • reactive oxygen species

ASJC Scopus subject areas

  • General Medicine


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