Impact of oxidized LDL/LOX-1 system on ligamentum flavum hypertrophy

Sota Nagai, Kurenai Hachiya, Hiroki Takeda, Daiki Ikeda, Soya Kawabata, Kota Watanabe, Shinjiro Kaneko, Nobuyuki Fujita

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Patients with lumbar spinal canal stenosis (LSS) often have peripheral arterial disease and aortic disease based on atherosclerosis. Oxidized LDL, which is clinically involved in the development of atherosclerosis, may also influence LF hypertrophy, but the function of the oxidized low-density lipoprotein (LDL)/lectin-type oxidized LDL receptor 1 (LOX-1) system in LF hypertrophy is unknown. We aimed to elucidate the potential involvement of oxidized LDL/LOX-1 system in ligamentum flavum (LF) hypertrophy. Methods: A total of 43 samples were collected from LF tissues of the patients who underwent posterior lumbar spinal surgery. Immunohistochemistry for LOX-1 was performed using human LF samples. We treated the cells in vitro with inflammatory cytokines TNF-α and IL-1β, oxidized LDL, and simvastatin. The expressions of LOX-1 and LF hypertrophy markers including type I collagen, Type III collagen, and COX-2 were assessed by real-time RT-PCR and immunocytochemistry. Phosphorylation of MAPKs and NF-κb was evaluated by Western blot after treatment with TNF-α, IL-1β, oxidized LDL, and simvastatin. Results: A significant weak correlation was observed between the number of positive cells of LOX-1 and cross-sectional area of LF on preoperative axial magnetic resonance imaging. In functional analysis, simvastatin treatment neutralized the oxidized LDL-mediated induction of mRNA expressions of LF hypertrophy markers. Western blot analysis showed that oxidized LDL as well as TNF-α and IL-1β activated the signaling of MAPKs and NF-κb in LF cells, and that simvastatin treatment reduced the phosphorylation of all signaling. The TNF-α and IL-1β treatments increased both mRNA and protein expression of LOX-1 in LF cells. Conclusion: We found a link between the oxidized LDL/LOX-1 system and LF hypertrophy. In addition, our in vitro analysis indicate that oxidized LDL may affect LF hypertrophy through signaling of MAPKs. Our results suggest that the oxidized LDL/LOX-1 system may be a potential therapeutic target for LSS.

Original languageEnglish
JournalJournal of Orthopaedic Science
DOIs
Publication statusAccepted/In press - 2022

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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