Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies

Abstract

Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

N-Cadherin-Mediated Activation of PI3K/Akt-GSK-3β Signaling Attenuates Nucleus Pulposus Cell Apoptosis Under High-Magnitude Compression

“…The chronic and progressive matrix degradation is the main pathological character during disc degeneration [30, 31]. Cell apoptosis-induced decrease in NP cell number is the direct reason for the decrease in the NP matrix synthesis [6, 9, 32].…”

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

“…IDD is a complex disease process that begins with changes in the local cellular microenvironment and progresses to impairment of their structure and function [59]. Although the pathogenesis is not fully understood, it has been well established that ECM disruption, inflammatory responses, apoptosis, autophagy, and cell proliferation play critical roles in promoting the development of disc degeneration [60][61][62][63].…”

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

“…IVDs play an important role in load bearing, absorption and transmission between two adjacent vertebral bones [11], which mainly depends on the matrix homeostasis within the NP region. IDD is proposed to originate in the NP region, which is characterized by a decrease in the NP cell density and normal extracellular matrix content (i.e., proteoglycan and collagen II) [12, 13]. All these cellular and molecular changes can lead to NP dehydration and thus weaken the disc capacity to absorb compression [14].…”