Abstract
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.
Highlights
Intervertebral discs are pads of fibrocartilage, located between the vertebral body of the spine with degenerative changes, which are a major cause for back pain associated with aging [1]
The nucleus pulposus cell (NPC) of rats in the Intervertebral disc degeneration (IDD) group presented with proliferated intervertebral disc chondrocytes, disorderly arranged cartilage taking the place for fibrous plate, trabecular bone formation, blurred nucleus pulposus, and degenerated intervertebral disc
Our study was conducted aiming to investigate the ability of small ubiquitin-related modifier 2 (SUMO2) gene silencing in the stimulation of the proliferation, apoptosis, and senescence of NPCs through the p53 signaling pathway mediation in IDD rats
Summary
Intervertebral discs are pads of fibrocartilage, located between the vertebral body of the spine with degenerative changes, which are a major cause for back pain associated with aging [1]. Intervertebral disc degeneration (IDD) is regarded as a complex process accompanied by age-related change and tissue damage caused by stress, which is closely related to the promotion of cellular senescence, inflammatory response and catabolic metabolism, and reduced proliferation [2]. IDD, which is known to be asymptomatic in many cases, is closely associated with disc herniation, spinal stenosis, and radicular pain resulting from imbalance between catabolic and anabolic responses [3,4]. The SUMO2 protein family is a family of 17 kDa in mammals and one member in the yeast Saccharomyces cerevisiae, which has a functional value in the regulation of a large number of target molecules [8]. The results from the present study revealed that SUMO2 gene silencing mediated the p53 signaling pathway to ameliorate or postpone IDD by promoting the proliferation of nucleus pulposus cells
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