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Review
. 2018 Apr 7;3(1):1-11.
doi: 10.22603/ssrr.2017-0095. eCollection 2019 Jan 25.

Molecular Mechanisms of Intervertebral Disc Degeneration

Sean M Rider  1 , Shuichi Mizuno  1 , James D Kang  1
Affiliations
Review

Molecular Mechanisms of Intervertebral Disc Degeneration

Sean M Rider et al. Spine Surg Relat Res. .

Abstract

Intervertebral disc degeneration is a well-known cause of disability, the result of which includes neck and back pain with associated mobility limitations. The purpose of this article is to provide an overview of the known molecular mechanisms through which intervertebral disc degeneration occurs as a result of complex interactions of exogenous and endogenous stressors. This review will focus on some of the identified molecular changes leading to the deterioration of the extracellular matrix of both the annulus fibrosus and nucleus pulposus. In addition, we will provide a summation of our current knowledge supporting the role of associated DNA and intracellular damage, cellular senescence's catabolic effects, oxidative stress, and the cell's inappropriate response to damage in contributing to intervertebral disc degeneration. Our current understanding of the molecular mechanisms through which intervertebral disc degeneration occurs provides us with abundant insight into how physical and chemical changes exacerbate the degenerative process of the entire spine. Furthermore, we will describe some of the related molecular targets and therapies that may contribute to intervertebral repair and regeneration.

Keywords: DNA damage; Intervertebral disc; annulus fibrosus; cellular senescence; degeneration; inflammation; nucleus pulposus; oxidative stress.

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Conflict of interest statement

Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

Figures

Figure 1.
Figure 1.
Factors Contributing to Intervertebral Disc Degeneration. Demonstration of the multifactorial contributions to Intervertebral Disc Degeneration (IDD) including alterations of spine mechanics, Nucleus Pulposus (NP) & Annulus Fibrosus (AF) degeneration, DNA damage, Cellular Senescence and Oxidative Stress & Deregulated signaling. Extracellular Matrix (ECM), Stress-induced Premature Senescence (SIPS), Matrix Metalloproteinases (MMPs), Advanced Glycation End Productions (AGEs), and Reactive Oxygen Species (ROS).
Figure 2.
Figure 2.
Stress-Induced Premature Senescence Catabolic Effects. Illustrating the stepwise formation and subsequent catabolic effects of stress-induced premature senescence (SIPS).
Figure 3.
Figure 3.
Pathways Contributing to Intervertebral Disc Degeneration. Demonstrating two pathways - inflammation and oxidation - that contribute to intervertebral disc degeneration. Reactive Oxygen Species (ROS), Advanced Glycation End Productions (AGEs).
Figure 4.
Figure 4.
Activation of MAPKs Pathway. Illustrating one of the roles that inflammation and MAPK pathway play in contributing to intervertebral disc degeneration (IDD), and a possible method of hindering IDD by preventing the activation of the MAPK pathway.
See this image and copyright information in PMC

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