Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China.
Department of Orthopedics, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222061, P.R. China.
Int J Mol Med. 2021 Feb;47(2):688-698. doi: 10.3892/ijmm.2020.4809. Epub 2020 Dec 3.
Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein‑protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.
黄韧带肥厚（LFH）是椎管狭窄和后纵韧带骨化的重要原因。尽管许多研究都集中在导致 LFH 的机制上，但细胞机制仍知之甚少。本研究旨在探讨差异表达基因（DEGs）在 LFH 中的作用，阐明导致 LFH 的机制，并为进一步研究提供潜在的治疗靶点。从基因表达综合数据库（GEO）下载 GSE113212 数据集。分析微阵列数据，获得 DEGs。采用基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集和蛋白质-蛋白质相互作用（PPI）网络分析等生物信息学方法，获得关键基因和信号通路。此外，培养肥大的黄韧带细胞，并通过体外细胞生物学和分子生物学实验鉴定韧带细胞中的关键基因和信号通路。筛选出 2123 个基因作为 DEGs。在这些 DEGs 中，1384 个基因上调，739 个基因下调。KEGG 通路分析显示，DEGs 主要富集在 PI3K/AKT 信号通路中，PPI 网络分析筛选出 A 型整合素金属蛋白酶 10（ADAM10）为关键基因。体外实验验证表明，ADAM10 通过激活 PI3K/AKT 通路促进黄韧带细胞的增殖，导致黄韧带肥大。总体而言，体外实验结果表明，ADAM10 通过激活 PI3K/AKT 通路促进黄韧带细胞的增殖，这可能是 LFH 的发病机制之一。本研究的结果可能为进一步研究 LFH 的细胞机制提供基础和方向，并为潜在的新型治疗靶点和临床方法提供依据。
