Role of Nrf2 and HO-1 in intervertebral disc degeneration

Connect Tissue Res. 2022 Nov;63(6):559-576. doi: 10.1080/03008207.2022.2089565. Epub 2022 Jun 23.


Intervertebral disc degeneration (IDD) is a common age-related disease with clinical manifestations of lumbar and leg pain and limited mobility. The pathogenesis of IDD is mainly mediated by the death of intervertebral disc (IVD) cells and the imbalance of extracellular matrix (ECM) synthesis and degradation. Oxidative stress and inflammatory reactions are the important factors causing this pathological change. Therefore, the regulation of reactive oxygen species and production of inflammatory factors may be an effective strategy to delay the progression of IDD. In recent years, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream regulated protein heme oxygenase-1 (HO-1) have received special attention due to their antioxidant, anti-inflammatory and anti-apoptotic protective effects. Recent studies have elucidated the important role of these two proteins in the treatment of IDD disease. However, Nrf2 and HO-1 have not been systematically reported in IDD-related diseases. Therefore, this review describes the biological characteristics of Nrf2 and HO-1, the relationship between Nrf2- and HO-1-regulated oxidative stress and the inflammatory response and IDD, and the progress in research on some extracts targeting Nrf2 and HO-1 to improve IDD. Understanding the role and mechanism of Nrf2 and HO-1 in IDD may provide novel ideas for the clinical treatment and development of Nrf2- and HO-1-targeted drugs.

Keywords: HO-1; Intervertebral disc degeneration; Nrf2; inflammatory reaction; oxidative stress.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use
  • Heme Oxygenase-1 / metabolism
  • Heme Oxygenase-1 / therapeutic use
  • Humans
  • Intervertebral Disc Degeneration* / pathology
  • Intervertebral Disc* / pathology
  • NF-E2-Related Factor 2 / metabolism
  • NF-E2-Related Factor 2 / therapeutic use
  • Nucleus Pulposus* / pathology
  • Reactive Oxygen Species / metabolism


  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Heme Oxygenase-1