Wei Xiaodong, Yu Chao, Wang Jingjie
The Second Department of Spine Surgery, Yantaishan Hospital, Yantai, Shandong, China.
Connect Tissue Res. 2025 Jul;66(4):298-310. doi: 10.1080/03008207.2025.2508841. Epub 2025 May 23.
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.
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).
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.
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.
椎间盘退变（IDD）是一种导致腰痛的脊柱疾病。据报道，佩利诺E3泛素蛋白连接酶1（PELI1）的表达与炎症和细胞死亡相关。本研究旨在确定其在IDD中的潜在作用。
采用细胞计数试剂盒-8检测、5-乙炔基-2'-脱氧尿苷染色、衰老相关β-半乳糖苷酶染色、形态学观察、乳酸脱氢酶（LDH）释放检测、定量逆转录聚合酶链反应和蛋白质免疫印迹法，研究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。
PELI1在TNF-α处理的hNPCs中高表达。TNF-α处理显著降低了hNPCs的活力和增殖，但增强了衰老（p16和p21表达升高）、细胞外基质退变（胶原蛋白II和聚集蛋白聚糖表达降低，基质金属蛋白酶-13和含血小板反应蛋白基序的解聚素和金属蛋白酶-5表达上调）、核苷酸结合寡聚化结构域样受体家族含吡啉结构域蛋白3（NLRP3）炎性小体形成（NLRP3、含半胱天冬酶募集结构域的凋亡相关斑点样蛋白（ASC）和裂解的半胱天冬酶1表达增强）、细胞焦亡（裂解的gasdermin D表达升高）、LDH释放以及炎性细胞因子释放（高迁移率族蛋白B1、白细胞介素（IL）-1β和IL-18）。PELI1沉默可明显减轻这些作用，而其过表达则增强这些作用。有趣的是，ASC过表达可部分逆转PELI1沉默所引发的作用。
PELI1可能通过加速髓核细胞死亡促进IDD进展，并参与髓核细胞中由NLRP3炎性小体调节的炎症反应。这些表明PELI1是治疗IDD的潜在治疗靶点。
