Abstract
BackgroundEnvironmental and endogenous factors under genetic predisposition are considered to initiate the human intervertebral disc (IVD) degeneration. DNA methylation is an essential mechanism to ensure cell-specific gene expression for normal development and tissue stability. Aberrant epigenetic alterations play a pivotal role in several diseases, including osteoarthritis. However, epigenetic alternations, including DNA methylation, in IVD degeneration have not been evaluated. The purpose of this study was to comprehensively compare the genome-wide DNA methylation profiles of human IVD tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration.MethodsHuman NP tissues were used in this study. The samples were divided into two groups: early stage degeneration (n = 8, Pfirrmann’s MRI grade: I-III) and advanced stage degeneration (n = 8, grade: IV). Genomic DNA was processed for genome-wide DNA methylation profiling using the Infinium MethylationEPIC BeadChip array. Extraction of raw methylation data, clustering and scatter plot of each group values of each sample were performed using a methylation module in GenomeStudio software. The identification of differentially methylated loci (DMLs) and the Gene Ontology (GO) analysis were performed using R software with the ChAMP package.ResultsUnsupervised hierarchical clustering revealed that early and advanced stage degenerated IVD samples segregated into two main clusters by their DNA methylome. A total of 220 DMLs were identified between early and advanced disc degeneration stages. Among these, four loci were hypomethylated and 216 loci were hypermethylated in the advanced disc degeneration stage. The GO enrichment analysis of genes containing DMLs identified two significant GO terms for biological processes, hemophilic cell adhesion and cell-cell adhesion.ConclusionsWe conducted a genome-wide DNA methylation profile comparative study and observed significant differences in DNA methylation profiles between early and advanced stages of human IVD degeneration. These results implicate DNA methylation in the process of human IVD degeneration.
Highlights
Low back pain (LBP) is a debilitating disorder that is significantly associated with personal, social, and economic burdens
Unsupervised hierarchical clustering revealed that early and advanced stage degenerated intervertebral disc (IVD) samples segregated into two main clusters by their DNA methylome
DNA methylome in early and advanced stages of human intervertebral disc degeneration Unsupervised hierarchical clustering revealed that early and advanced stages of degenerated samples segregated into two main clusters by their DNA methylome (Fig 2)
Summary
Low back pain (LBP) is a debilitating disorder that is significantly associated with personal, social, and economic burdens. IVD degeneration, especially NP degeneration, is well characterized by a change in extracellular matrix molecules (loss of proteoglycan and water content in the NP), resulting in an alteration of the biomechanical properties of IVD tissues. These degenerative changes are considered to induce the disruption of IVD tissues, leading to the degenerative disc diseases that are associated with low back pain[9]. The purpose of this study was to comprehensively compare the genome-wide DNA methylation profiles of human IVD tissues, nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration
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