PELI1 silencing delays intervertebral disc degeneration by impeding nucleus pulposus cell death.

IF 2.1 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI:10.1080/03008207.2025.2508841

Xiaodong Wei, Chao Yu, Jingjie Wang

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引用次数: 0

Abstract

Purpose: Intervertebral disc degeneration (IDD) is a spinal condition that causes low back pain. Pellino E3 ubiquitin protein ligase 1 (PELI1) expression reportedly correlates with inflammation and cell death. This study aimed to determine its potential role in IDD.

Methods: Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, senescence-associated β-galactosidase staining, morphological observation, lactate dehydrogenase (LDH) release assay, quantitative reverse transcriptase polymerase chain reaction, and western blotting were used to examine the effect of PELI1 on tumor necrosis factor alpha (TNF-α)-induced human primary nucleus pulposus cells (hNPCs).

Results: PELI1 was highly expressed in TNF-α-treated hNPCs. TNF-α treatment notably reduced hNPCs viability and proliferation, but enhanced senescence (elevated p16 and p21 expression), extracellular matrix degeneration (reduced collagen II and aggrecan expression and upregulated matrix metallopeptidase-13 and a disintegrin and metalloproteinase with thrombospondin type 1 motifs-5 expression), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome formation (enhanced NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and cleaved caspase 1 expression), pyroptosis (elevated cleaved gasdermin D expression), LDH release, and inflammatory cytokine release (high mobility group box 1, interleukin (IL)-1β, and IL-18). These effects were distinctly reduced by PELI1 silencing but enhanced by its overexpression. Interestingly, the effects triggered by PELI1 silencing were partially reversed by ASC overexpression.

Conclusions: PELI1 May promote IDD progression by expediting nucleus pulposus cell death and participates in the inflammatory response regulated by the NLRP3 inflammasome in nucleus pulposus cells. These suggest PELI1 as a potential therapeutic target for the treatment of IDD.

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PELI1沉默通过阻碍髓核细胞死亡延缓椎间盘退变。

目的：椎间盘退变（IDD）是一种引起腰痛的脊柱疾病。据报道，Pellino E3泛素蛋白连接酶1 （PELI1）表达与炎症和细胞死亡有关。本研究旨在确定其在缺乏症中的潜在作用。方法：采用细胞计数试剂盒-8法、5-乙基-2′-脱氧尿苷染色法、衰老相关β-半乳糖苷酶染色法、形态学观察、乳酸脱氢酶（LDH）释放法、定量逆转录酶聚合酶链反应法和western blotting检测PELI1对肿瘤坏死因子α (TNF-α)诱导的人原代髓核细胞（hNPCs）的影响。结果：PELI1在TNF-α处理的hNPCs中高表达。TNF-α治疗显著降低了hNPCs的活力和增殖，但增强了衰老（p16和p21表达升高）、细胞外基质变性（降低了II型胶原和聚集蛋白表达，上调了基质金属肽酶-13和具有血小板反应蛋白1型基元-5表达的分解素和金属蛋白酶）、核苷酸结合寡聚化结构域样受体家族含pyrin结构域-3 （NLRP3）炎性体形成(增强了NLRP3、凋亡相关斑点样蛋白含有caspase募集结构域（ASC）和裂解caspase 1表达)，焦亡（裂解gasdermin D表达升高），LDH释放和炎症细胞因子释放（高迁移率组1，白细胞介素(IL)-1β和IL-18）。沉默PELI1明显降低了这些影响，但过表达则增强了这些影响。有趣的是，由PELI1沉默引发的效应被ASC过表达部分逆转。结论：PELI1可能通过加速髓核细胞死亡促进IDD进展，并参与髓核细胞NLRP3炎性体调控的炎症反应。这些提示PELI1是治疗IDD的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.