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.

• Authors: Qunhu Zhang, Jie Li, You Li, Hui Che, Ying Chen, Jianghui Dong, Cory J Xian, Dengshun Miao, Liping Wang, Yongxin Ren
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 16 Pg. 8950-8961 (08 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32583517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Aggrecans
• Antioxidants
• Bmi1 protein, mouse
• Interleukin-1beta
• Proto-Oncogene Proteins
• Tumor Necrosis Factor-alpha
• Collagen
• Superoxide Dismutase
• superoxide dismutase 2
• Polycomb Repressive Complex 1
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Aggrecans (metabolism)
• Animals
• Antioxidants (physiology)
• Apoptosis (drug effects)
• Collagen (metabolism)
• Interleukin-1beta (metabolism)
• Intervertebral Disc (drug effects, metabolism)
• Intervertebral Disc Degeneration (drug therapy, metabolism)
• Mice
• Organ Culture Techniques (methods)
• Oxidative Stress (drug effects)
• Polycomb Repressive Complex 1 (deficiency)
• Proto-Oncogene Proteins (deficiency)
• Superoxide Dismutase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)