Comprehensive analysis of N6-methyladenosine (m6A) modification during the degeneration of lumbar intervertebral disc in mice
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Updated: Jul 29, 2026
A Mouse Model of Lumbar Spine Instability
Published on: April 23, 2021
Bin Zhu1, Hao-Xiang Chen1, Shan Li1
1Department of Spine Surgery, The First Affiliated Hospital of University of South China, Hengyang, China.
Objective:
To study the N6-methyladenosine (m6A) modification pattern of nucleus pulposus (NP) tissue during intervertebral disc degeneration (IDD).
Methods:
A standing mouse model was generated, and staining and imaging methods were used to evaluate the IDD model. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) was used to analyze m6A methylation-associated transcripts in the NP, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of methylation-related enzymes and conduct bio-informatics analysis.
Results:
The standing mouse model caused IDD. Continuous axial pressure changed the expression of related methylases in degenerated NP tissue. Relative to the control group, the expression levels of KIAA1429, METTL14, METTL3, METTL4, WTAP, DGCR8, EIF3A and YTHDC1 in the experimental group were higher, while those of FTO, ELAVL1, HNRNPC1 and SRSF2 were lower. We identified 985 differentially expressed genes through MeRIP-Seq, among which 363 genes were significantly up-regulated, and 622 genes were significantly down-regulated. In addition, among the 9648 genes counted, 1319 m6A peaks with significant differences in methylation were identified, among which 933 were significantly up-regulated, and 386 were significantly down-regulated. Genes and pathways that were enriched in IDD have been identified.
Conclusion:
The results of this study elucidated the m6A methylation pattern of NP tissue in degenerated lumbar intervertebral disc of mice and provided new perspectives and clues for research on and the treatment of lumbar disc degeneration.
The Translational Potential Of This Article:
As one of the important causes of low back and leg pain, intervertebral disc degeneration brings a huge economic burden to the society, family and medical system. Therefore, understanding the molecular and cellular mechanisms of intervertebral disc degeneration is of great significance for guiding clinical treatment. In this study, methylated RNA immunoprecipitation with next-generation sequencing on mice lumbar nucleus pulposus tissues found that differentially expressed genes and changes in the expression of related methylases, confirming that RNA methylation is involved in intervertebral disc degeneration. The process provides new vision and clues for future research on intervertebral disc degeneration.
Insights
This study reveals the N6-methyladenosine (m6A) modification patterns in nucleus pulposus tissue during intervertebral disc degeneration (IDD) in mice. Findings highlight RNA methylation
Area of Science:
- Biochemistry
- Molecular Biology
- Genomics
Background:
- Intervertebral disc degeneration (IDD) is a major cause of low back pain, necessitating a deeper understanding of its molecular mechanisms.
- N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological processes, but its role in IDD remains largely unexplored.
Purpose of the Study:
- To investigate the m6A modification patterns in nucleus pulposus (NP) tissue during the progression of intervertebral disc degeneration (IDD).
- To identify key genes and pathways regulated by m6A methylation in the context of IDD.
Main Methods:
- Generation of a standing mouse model to induce IDD.
- Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) to profile m6A-associated transcripts in NP tissue.
- Quantitative real-time PCR (qRT-PCR) to assess the expression of methylation-related enzymes.
Main Results:
- The mouse model successfully replicated IDD, with altered expression of m6A methylases and demethylases in degenerated NP tissue.
- MeRIP-seq identified 985 differentially expressed genes and 1319 differentially methylated m6A peaks in IDD compared to control.
- Enrichment analysis revealed specific genes and pathways implicated in the pathogenesis of IDD.
Conclusions:
- This study elucidates the m6A methylation landscape in degenerated mouse NP tissue.
- The findings provide novel insights into the role of RNA methylation in IDD and suggest potential therapeutic targets.
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