ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Abstract

Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway

“…According to the free-radical theory of aging, oxidative stress initiated by ROS accumulation contributes to the functional decline that occurs during aging [8]. Generally, ROSs include the superoxide anion (O 2− ), nitric oxide (NO), and hydroxyl radicals (OH), which are byproducts of cell oxidative metabolism [29]. Once the intracellular ROS accumulation has exceeded the cell's capacity to scavenge, it can lead to oxidative damage and concomitant cellular damage.…”

Hydrogen peroxide induces programmed necrosis in rat nucleus pulposus cells through the RIP1/RIP3‐PARP‐AIF pathway

“…As a common trigger of oxidative stress in vitro, H 2 O 2 has been widely applied to investigate the underlying mechanisms in IVD cells death. Currently, it have been confirmed that apoptosis and autophagy participate in the H 2 O 2 ‐induced NP cell death . Nevertheless, there have been few studies about programmed necrosis or exploration of the relevant mechanisms in IVDD.…”

Molecular Mechanisms of Intervertebral Disc Degeneration

“…131 ROS is detrimental to the structural and functional homeostasis of the disc by causing the damage of lipids, DNA, and proteins. 132 Hydrogen peroxide, identified in human NP tissue, along with peroxisomes detected in AF cells in vitro, further support discs cells as ROS generators. 133,134 With mitochondrion dysfunction as a known source of excessive ROS production, the role of mitochondrion-dependent ROS has been described in various disc cells including human and rat NP and AF cells.…”