Cell death in intervertebral disc degeneration

Apoptosis. 2013 Jul;18(7):777-85. doi: 10.1007/s10495-013-0839-1.

Abstract

Degeneration of intervertebral disc (IVD) is mainly a chronic process of excessive destruction of the extracellular matrix (ECM), and also is thought to be the primary cause of low back pain. Presently, however, the underlying mechanism of IVD degeneration is still not elucidated. Cellular loss from cell death has been believed to contribute to the degradation of ECM and plays an important role in the process of IVD degeneration, but the mechanisms of cell death in degenerated IVD remain unclear. Apoptosis, a very important type of IVD cell death, has been considered to play a crucial role in the process of degeneration. Autophagy, a non-apoptosis death type of programmed cell death, has been considered extensively involved in many pathological and physiological processes, including the degenerative diseases. Thus, the research on cell death in IVD degeneration has become a new focus recently. In this review, by analyzing the available literature pertaining to cell death in IVD and discussing the inducing factors of IVD degeneration, NP cells and ECM in IVD degeneration, apoptotic signal transduction pathways involved in IVD cell death, the relationship of cell death with IVD degeneration and potential therapeutic strategy for IVD degeneration by regulating cell death, we conclude that different stimuli induce cell death in IVD via various signal transduction pathways, and that cell death may play a key role in the degenerative process of IVD. Regulation of cell death could be a potential and attractive therapeutic strategy for IVD degeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / agonists
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Caspase Inhibitors / pharmacology*
  • Caspases / genetics*
  • Caspases / metabolism
  • Cell Death / drug effects
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Gene Expression Regulation
  • Humans
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / pathology
  • Intervertebral Disc Degeneration / genetics
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology
  • Intervertebral Disc Degeneration / therapy*
  • Low Back Pain / prevention & control
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Stress, Mechanical
  • Transcription Factor CHOP / antagonists & inhibitors*
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Caspase Inhibitors
  • DDIT3 protein, human
  • RNA, Small Interfering
  • Transcription Factor CHOP
  • Caspases