Retraction: Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration

Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Therefore, in the present study, we investigated the effects of SUMO2 on proliferation and senescence of nucleus pulposus cells (NPCs) via mediation of p53 signaling pathway in rat models of IDD. Methods: After the establishment of rat models of IDD for the measurement of positive expression of SUMO2/3 protein, the mRNA and protein levels of SUMO2, molecular phenotype [matrix metalloproteinase-2 (MMP-2) and hypoxia-inducible factor-1α (HIF-1α)] and p53 signaling pathway-related genes [p21, murine double minute-2 (MDM2), growth arrest and DNA-damage-inducible protein 45 α (GADD45α), cyclin-dependent kinase 2/4 (CDK2/4), and CyclinB1] were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence. Results: The rat models of IDD were successfully constructed. The results obtained showed that there was a higher positive expression of SUMO2/3 protein in IDD rats. Moreover, the silencing of the SUMO2 gene decreases the levels of SUMO2, p53, p21, MDM2, GADD45α, MMP-2, and HIF-1α expressions and p53 phosphorylation level while it increases the levels of CDK2/4 and CyclinB1 expressions. In addition, SUMO2 gene silencing enhances proliferation and suppresses apoptosis and cell senescence of NPCs. Conclusion: In conclusion, SUMO2 gene silencing promotes proliferation, and inhibits the apoptosis and senescence of NPCs in rats with IDD through the down-regulation of the p53 signaling pathway. Thus, SUMO2 is a potential target in the treatment of IDD.

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Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-κB Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6632786 ◽

2021 ◽

Vol 2021 ◽

pp. 1-27

Author(s):

Haichao Yu ◽

Guowei Hou ◽

Jiankang Cao ◽

Yanyu Yin ◽

Yunpeng Zhao ◽

...

Keyword(s):

Intervertebral Disc ◽

Mitochondrial Dysfunction ◽

Signaling Pathway ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Intervertebral Discs ◽

Nucleus Pulposus Cells ◽

Mitochondrial Ros ◽

Tnf Α

Intervertebral disc degeneration (IVDD), one of the most common clinical diseases worldwide, causes disc herniation and sciatica. Recent studies have identified the involvement of mitochondrial dysfunction, inflammatory responses, and extracellular matrix degradation in IVDD. Mangiferin is known to protect against various diseases by inhibiting oxidative stress, suppressing inflammation reaction, and relieving mitochondrial dysfunction. Whether mangiferin can alleviate IVDD remains to be elucidated. In the present study, human nucleus pulposus cells (HNPCs) and mouse intervertebral discs were cultured and stimulated with TNF-α, with or without treatment of mangiferin. Moreover, we established a rat needle puncture model and injected mangiferin into the intervertebral discs to verify its protective effect on IVDD. Furthermore, the activity of the NF-κB signaling pathway was tested in vitro. Our results indicated that mangiferin alleviated the inflammatory response and reversed the loss of major intervertebral disc components. Besides, mangiferin reduced reactive oxygen species production, ameliorated mitochondrial damage, and decreased the expression of apoptosis-related parameters in stimulation of TNF-α. In addition, mangiferin antagonized the activation of the NF-κB signaling pathway induced by TNF-α. Collectively, mangiferin antagonized mitochondrial ROS in NP cells and protected against IVDD by suppressing the activation of the NF-κB signaling pathway, which might provide a potential therapeutic instrument for IVDD.

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The c‑Jun signaling pathway has a protective effect on nucleus pulposus cells in patients with intervertebral disc degeneration

Experimental and Therapeutic Medicine ◽

10.3892/etm.2020.9251 ◽

2020 ◽

Vol 20 (5) ◽

pp. 1-1

Author(s):

Ming Lei ◽

Kun Wang ◽

Shuai Li ◽

Kangcheng Zhao ◽

Wenbin Hua ◽

...

Keyword(s):

Intervertebral Disc ◽

Protective Effect ◽

Signaling Pathway ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Nucleus Pulposus Cells

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MiR-25 Protects Against Apoptosis of Nucleus Pulposus Cells by Targeting SUMO2 in Intervertebral Disc Degeneration

10.21203/rs.3.rs-63482/v1 ◽

2020 ◽

Author(s):

Lei Changbin ◽

Li Jiang ◽

Tang Guang ◽

Wang Jiong ◽

Hongsheng Lin

Keyword(s):

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Luciferase Reporter ◽

Nucleus Pulposus Cells ◽

P53 Signaling ◽

Pulldown Assay ◽

Signaling Axis ◽

Incorporation Assay

Abstract Background MiR-25 was reported to be down-regulated in patients with intervertebral disc degeneration (IDD). However, the potential role of miR-25 in IDD remained unclear. Therefore, the present study aimed to investigate the effects of miR-25 on human intervertebral disc nucleus pulposus cells (NPCs).Methods We evaluated the expression of miR-25 and small ubiquitin-related modifier 2 (SUMO2) in human nucleus pulposus (NP) tissues by real-time PCR and western blotting. Then, the target relationship between miR-25 and SUMO2 was validated by luciferase reporter assay and biotin-coupled miRNA pulldown assay. The potential roles of miR-25 in NPC proliferation and apoptosis were confirmed using CCK-8 assay, EdU incorporation assay, and flow cytometry.Results MiR-25 was lowly expressed in the patients with IDD. In addition, miR-25 facilitated the growth of NPCs by increasing cell proliferation and inhibiting apoptosis. Furthermore, we elucidated that SUMO2 was a target gene of miR-25, and was regulated by miR-25 through p53 signaling pathway. Restore of SUMO2 expression abrogated the effects of miR-25 on NPCs.Conclusion MiR-25 promoted the proliferation, inhibited the apoptosis of NPCs, and suppressed the development of IDD via SUMO2-mediated p53 signaling axis.

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