Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment

Abstract

The transcriptional repressor Bmi‐1 is involved in cell‐cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi‐1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N‐acetylcysteine (NAC) on intervertebral disc degeneration. Bmi‐1 −/− mice were treated with the antioxidant NAC, supplied in drinking water (Bmi‐1 −/− +NAC). For in vitro experiments, mouse intervertebral discs were cultured under low oxygen tension and serum‐limiting conditions in the presence of tumour necrosis factor α and interleukin 1β in order to mimic degenerative insult. Disc metabolism parameters in these in vitro and in vivo studies were evaluated by histopathological, immunohistochemical and molecular methods. Bmi‐1 −/− mice showed lower collagen Ⅱ and aggrecan levels and higher collagen Ⅹ levels than wild‐type and Bmi‐1 −/− +NAC mice. Bmi‐1 −/− mice showed significantly lower superoxide dismutase (SOD)‐1, SOD‐2, glutathione peroxidase (GPX)‐1 and GPX‐3 levels than their wild‐type littermates and Bmi‐1 −/− + NAC mice. Relative to Bmi‐1 −/− mice, the control and Bmi‐1 −/− +NAC mice showed significantly lower p16, p21, and p53 levels. These results demonstrate that Bmi‐1 plays an important role in attenuating intervertebral disc degeneration in mice by inhibiting oxidative stress and cell apoptosis.

Effects of omega-3 fatty acids and CoQ10 on gross morphology of intervertebral discs subjected to immobilization

“…of disc degeneration was found to be significantly supplementation (Sanoobar et al, 2013;Santoro, 2020). This is in agreement with a study that argues that antioxidant therapy aids in stabilizing blood vessels and reduce oxidative damage caused from degeneration within the IVD (Zhang et al, 2020).…”

RETRACTED: MicroRNA-199a-5p accelerates nucleus pulposus cell apoptosis and IVDD by inhibiting SIRT1-mediated deacetylation of p21

“… 14 Also, reduced p21 levels induced by Bmi-1 are known to possess the potential to attenuate the progression of IVDD. 15 Based on the aforementioned evidence, we hypothesized that miR-199a-5p might be involved in the mediation of the nucleus pulposus cell apoptotic pathway via SIRT1-mediated p21, thus playing a regulatory role in the progression of IVDD. To confirm this hypothesis, we performed a series of experiments to investigate the correlation between miR-199a-5p, SIRT1, and p21 and characterize their roles in IVDD progression in enrolled IVDD-diagnosed patients and established rat IVDD models.…”

Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells

“…NAC is a key precursor to a variety of endogenous antioxidants that aid in the breakdown of peroxides and the suppression of oxidative stress by supplying cellular glutathione. In our previous studies, the antioxidant NAC treatment inhibited the Bmi-1 gene deficiency-caused oxidative stress and IDD progress in mice [10], and deletion p16 also attenuated the mechanical force-12…”

“…Based on our previous studies, excessive accumulation of reactive oxygen species (ROS) leads to a high level of oxidative stress, which causes DNA damage, breaks up the cell cycle, and disorders the ECM metabolism in NP cells [6]. Moreover, the N-acetylcysteine (NAC, an antioxidant) supplementation or Cdkn2a gene deletion can delay NP cell senescence via regulating oxidative stress [10]. Therefore, we screened for oxidative stress-related genes from the observed 1057 DEGs and noticed polyamine oxidase (PAOX) was upregulated in the degenerated disc tissues.…”