Pathogenesis and therapeutic implications of matrix metalloproteinases in intervertebral disc degeneration: A comprehensive review

Biochimie. 2023 Nov;214(Pt B):27-48. doi: 10.1016/j.biochi.2023.05.015. Epub 2023 May 31.

Abstract

Intervertebral disc (IVD) degeneration (IDD) is a common disorder that affects the spine and is a major cause of lower back pain (LBP). The extracellular matrix (ECM) is the structural foundation of the biomechanical properties of IVD, and its degradation is the main pathological characteristic of IDD. Matrix metalloproteinases (MMPs) are a group of endopeptidases that play an important role in the degradation and remodeling of the ECM. Several recent studies have shown that the expression and activity of many MMP subgroups are significantly upregulated in degenerated IVD tissue. This upregulation of MMPs results in an imbalance of ECM anabolism and catabolism, leading to the degradation of the ECM and the development of IDD. Therefore, the regulation of MMP expression is a potential therapeutic target for the treatment of IDD. Recent research has focused on identifying the mechanisms by which MMPs cause ECM degradation and promote IDD, as well as on developing therapies that target MMPs. In summary, MMP dysregulation is a crucial factor in the development of IDD, and a deeper understanding of the mechanisms involved is needed to develop effective biological therapies that target MMPs to treat IDD.

Keywords: Extracellular matrix; Intervertebral disc degeneration; Matrix metalloproteinases.

Publication types

  • Review

MeSH terms

  • Extracellular Matrix / metabolism
  • Humans
  • Intervertebral Disc Degeneration* / drug therapy
  • Intervertebral Disc Degeneration* / metabolism
  • Intervertebral Disc Degeneration* / pathology
  • Intervertebral Disc* / metabolism
  • Intervertebral Disc* / pathology
  • Matrix Metalloproteinases / metabolism
  • Transcriptional Activation
  • Up-Regulation

Substances

  • Matrix Metalloproteinases