MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration

Biomed Pharmacother. 2021 Nov:143:112170. doi: 10.1016/j.biopha.2021.112170. Epub 2021 Sep 15.

Abstract

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.

Keywords: Apoptosis; Extracellular matrix (ECM); Intervertebral disc degeneration (IDD); MAPK/ERK pathway; Senescence.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / enzymology
  • Extracellular Matrix / pathology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / enzymology
  • Intervertebral Disc / pathology
  • Intervertebral Disc / physiopathology
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / enzymology
  • Intervertebral Disc Degeneration / pathology
  • Intervertebral Disc Degeneration / physiopathology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Protein Kinase Inhibitors
  • Extracellular Signal-Regulated MAP Kinases