P53 is an apoptosis marker which is involved in determining nucleus pulposus (NP) cell fate. Little is known about P53 interaction with N-Myc downstream-regulated gene 2 (NDRG2) in intervertebral disc degeneration (IVDD). Here, we studied the role of the P53-NDRG2 axis in IVDD. We found that NDRG2 was expressed in NP tissue obtained from patients with IVDD. The level of NDRG2 was positively related to the severity of IVDD, as determined by Pfirrmann grading. Subsequently, we overexpressed NDRG2 in human NP cells by adenoviral transfection and studied the effects of increased levels of NDRG2 on the viability and apoptosis of these cells. NDRG2 overexpression induced NP cell apoptosis and reduced viability in NP cells obtained from patient with IVDD. We also found that the level of P53 was elevated in NP cells from patients with IVDD and treatment with exogenous P53 upregulated NDRG2 in NP cells. Last, IVDD model was established in P53 knockout mice and the pathological changes in the intervertebral discs and NDRG2 expression were examined. P53 knockout can reduce the damage of NP tissues after IVDD surgery to some extent. Restoration of NDRG2 antagonized the effect of P53 knockout on IVDD. Collectively, this study suggests that elevated P53 in NP cells stimulates apoptosis of the cells by upregulating NDRG2 expression, thereby exacerbating IVDD.

中文翻译：

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P53上调通过上调NDRG2促进椎间盘退变中髓核细胞凋亡

P53 是一种凋亡标志物，参与确定髓核 (NP) 细胞的命运。关于 P53 与 N-Myc 下游调节基因 2 (NDRG2) 在椎间盘退变 (IVDD) 中的相互作用知之甚少。在这里，我们研究了 P53-NDRG2 轴在 IVDD 中的作用。我们发现 NDRG2 在从 IVDD 患者获得的 NP 组织中表达。NDRG2 的水平与 IVDD 的严重程度呈正相关，由 Pfirrmann 分级确定。随后，我们通过腺病毒转染在人 NP 细胞中过表达 NDRG2，并研究了 NDRG2 水平升高对这些细胞活力和凋亡的影响。NDRG2 过表达诱导 NP 细胞凋亡并降低从 IVDD 患者获得的 NP 细胞的活力。我们还发现 IVDD 患者的 NP 细胞中 P53 水平升高，外源性 P53 治疗上调 NP 细胞中的 NDRG2。最后，在P53基因敲除小鼠中建立IVDD模型，检测椎间盘的病理变化和NDRG2的表达。P53敲除可在一定程度上减轻IVDD手术后NP组织的损伤。NDRG2 的恢复拮抗 P53 敲除对 IVDD 的影响。总的来说，这项研究表明，NP 细胞中升高的 P53 通过上调 NDRG2 的表达来刺激细胞凋亡，从而加剧 IVDD。P53敲除可在一定程度上减轻IVDD手术后NP组织的损伤。NDRG2 的恢复拮抗 P53 敲除对 IVDD 的影响。总的来说，这项研究表明，NP 细胞中升高的 P53 通过上调 NDRG2 的表达来刺激细胞凋亡，从而加剧 IVDD。P53敲除可在一定程度上减轻IVDD手术后NP组织的损伤。NDRG2 的恢复拮抗 P53 敲除对 IVDD 的影响。总的来说，这项研究表明，NP 细胞中升高的 P53 通过上调 NDRG2 的表达来刺激细胞凋亡，从而加剧 IVDD。