Analysis of key genes and pathways associated with the pathogenesis of intervertebral disc degeneration

Abstract

Background: Intervertebral disc degeneration (IDD) is widely known as the main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. This study aims to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD. Material/methods: The gene expression data of GSE23130 was downloaded, and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. Also, protein-protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module. Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs were mainly enriched in the regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most DEGs were primarily enriched in the PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1. Conclusions: In summary, key candidate genes and pathways were identified by using integrated bioinformatics analysis, which may provide insights into the underlying mechanisms and offer potential target genes for the treatment of IDD.

The Role of Polymorphisms in Collagen-Encoding Genes in Intervertebral Disc Degeneration

“…Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity [ 36 ] ( Table 1 ) and the role of SNVs of this gene in the development of IVDD is doubtful and insufficiently studied. This may be due to the lower expression of the COL1A2 gene compared to COL1A1 in IVD structures [ 37 , 38 ].…”

Lumican silencing alleviates tumor necrosis factor-α-induced nucleus pulposus cell inflammation and senescence by inhibiting apoptosis signal regulating kinase 1/p38 signaling pathway via inactivating Fas ligand expression

“…As an important extracellular matrix glycoprotein in human cartilage tissues, LUM has been demonstrated to be highly expressed in the NP specimens from human herniated lumbar discs [ 13 ]. However, the role of LUM in the progression of IDD remains to be elucidated.…”

“…LUM has been recently reported to be expressed at a differentially high level in the NP specimens from human herniated lumbar discs [ 13 ]. In osteoarthritis, overexpressed LUM has a proven association with the cartilage degradation and macrophage polarization [ 16 ].…”

“…Lumican (LUM), an important extracellular matrix glycoprotein in human cartilage tissues, has been recently reported to be expressed at a differentially high level in the NP specimens from human herniated lumbar discs [ 13 ]. A study in 1999 has corroborated a senescence-related increase in LUM in the lumbar intervertebral discs obtained from patients of varying ages [ 14 ].…”

Perspectives of targeted therapy for nonspecific back pain: a review of recent publications

“…В поиске ключевых генов и путей развития дегенеративных изменений дисков [15] проанализировали массив данных GSE23130, используя методы биоинформатики, и индентифицировали 30 подавляющих генов (downregulated) и 79 активирующих (upregulated). Дифференциально экспрессируемые гены участвовали в регуляции катаболизма белков, организации межклеточного матрикса, организации коллагеновых фибрилл, экстрацеллюлярной структурной организации.…”