Oxidative stress participates in age-related changes in rat lumbar intervertebral discs

Intervertebral disc degeneration (DD) is a cause of low back pain (LBP) in some individuals. However, while >30% of adults have DD, LBP only develops in a subset of individuals. To gain insight into the mechanisms underlying non-painful versus painful DD, human cerebrospinal fluid (CSF) was examined using differential expression shotgun proteomic techniques comparing healthy controls, subjects with non-painful DD, and patients with painful DD scheduled for spinal fusion surgery. Eighty-eight proteins were detected, 27 of which were differentially expressed. Proteins associated with DD tended to be related to inflammation (e.g. cystatin C) regardless of pain status. In contrast, most differentially expressed proteins in DD-associated chronic LBP patients were linked to nerve injury (e.g. hemopexin). Cystatin C and hemopexin were selected for further examination by ELISA in a larger cohort. While Cystatin C correlated with DD severity but not pain or disability, hemopexin correlated with pain intensity, physical disability and DD severity. This study demonstrates that CSF can be used to study mechanisms underlying painful DD in humans, and suggests that while painful DD is associated with nerve injury, inflammation itself is not sufficient to develop LBP.

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“…In agreement, animal models have demonstrated that superoxide dismutase levels decrease in age-related intervertebral DD. 49 …”

Section: Discussionmentioning

confidence: 99%

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

Lim

Anderson

Hari

et al. 2017

The Journal of Pain

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“…Mounting evidences have suggested that NO and PGE2 serve crucial roles in the modulation of cellular metabolism of discs and the pathology of IDD (18)(19)(20). PGE2 was found to be involved in the progression of sciatica (21).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

Shen

Han

et al. 2018

Exp Ther Med

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Abstract. Low back pain (LBP) is one of the most common musculoskeletal diseases in the world. The incidence is ~70% in adults and many of them suffer from disability. Recently, intervertebral disc degeneration (IDD) has been deemed as a main cause of LBP. The present study aimed to investigate the potentials of growth and differentiation factor-5 (GDF-5) in IDD. The protein levels of prostaglandin-E2 (PGE2), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in culture medium were evaluated by ELISA. mRNA and protein expression levels in nucleus pulposus (NP) cells were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. Griess reaction was applied to test the nitric oxide (NO) concentration in the culture supernatant. The expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in NP cells were measured by RT-qPCR. Collagen-II, aggrecan, IκBα and phosphorylated (p)-p65 expression levels were detected by western blotting. Compared with the control group, protein expression levels of TNF-α, IL-1β and PGE2, and NO concentration in culture medium were upregulated by LPS, which were significantly repressed by GDF-5 overexpression (P<0.05). Additionally, GDF-5 overexpression reduced lipopolysaccharide-induced upregulation of TNF-α, IL-1β, iNOS, COX-2, collagen-II, aggrecan, IκBα and p-p65 expression levels in NP cells. IntroductionLow back pain (LBP) is one of the most common musculoskeletal diseases in the world, with an incidence of ~70% in adults (1). Unfortunately, many of those with LBP suffer from disability (1). Multiple causes could lead to LBP; however, intervertebral disc degeneration (IDD) and disc herniation are reported to be the two most common diagnoses and targets for intervention (2), with IDD being deemed as the main cause of LBP (3,4). IDD is a multifactorial process that is characterized by cellular and biochemical changes in the disc tissue, consequently generating structural failure (5).A normal disc is composed of two types of tissues, the nucleus pulposus (NP) and the annulus fibrosus (AF), and they serve different roles in load bearing. Gelatinous NP is predominantly composed of type II collagen and proteoglycans, and its relatively higher water content (compared to AF tissues) is responsible for its resistance to compressive forces and hydrostatic pressurization (6,7). In degeneration, loss of proteoglycans and water signal intensity is detected by changes in disc height and T2-weighted magnetic resonance imaging (MRI) signal in the NP (8), which may lead to redistribution of load onto fibrochondrocyte-like cells in the AF (9).As IDD is associated with normal aging, many people with IDD indications on MRI do not suffer with pain or disability (10,11). However, current treatments for IDD, including surgery, steroid injection and physical therapy, treat symptoms and not disc structure/function regeneration.Inflammation is correlated with IDD and it involves various cells and molecules (12). Multiple g...

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“…The level of NO in rat degenerative discs was shown to increase dramatically [16]. Peroxynitrite, a potent oxidative agent derived from the interaction of O 2 − and NO in vivo, can cause tyrosine nitrosylation that is a marker of excessive ROS production [70].…”

Section: Disturbed Redox Homeostasis In the Microenvironment Of Dementioning

confidence: 99%

“…Recent studies have reported that the establishment and progression of IDD are tightly associated with reactive oxygen species (ROS) and oxidative stress [14–16]. Although the roles of ROS and oxidative stress in various diseases have been widely investigated, including cardiovascular diseases, diabetes, and osteoarthritis [17–19], little attention has been paid to the effect of oxidative stress on the structure and function of IVDs until now.…”

Section: Introductionmentioning

confidence: 99%

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

Feng

Yang

Lan

et al. 2017

Oxidative Medicine and Cellular Longevity

293

262

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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.

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Oxidative stress participates in age-related changes in rat lumbar intervertebral discs

Cited by 107 publications

References 29 publications

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

Evidence for a Role of Nerve Injury in Painful Intervertebral Disc Degeneration: A Cross-Sectional Proteomic Analysis of Human Cerebrospinal Fluid

Overexpression of growth and differentiation factor-5 inhibits inflammatory factors released by intervertebral disc cells

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

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