ArticleClinical and translational medicine2022
m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Epigenetic Factors Related to Low Back Pain: A Systematic Review of the Current Literature.International journal of molecular sciences · 2023Pooled it
- Epigenetic research methods and animal models for intervertebral disc degeneration (Review).Molecular medicine reports · 2026Review
- mMolecular medicine reports · 2026Review
- A continuous DNA repairing system for alleviating intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Epigenetic crossroads in intervertebral disc degeneration: Unlocking novel therapeutic avenues (Review).Molecular medicine reports · 2026Review
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- METTL3-mediated GLUD1 m6A Modification Promotes Hydrogen Peroxide-induced Mitochondrial Dysfunction in Human Nucleus Pulposus Cells Via the Glutamate/α-KG Metabolic Axis.Journal of musculoskeletal & neuronal interactions · 2026Article
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- KDM4A-induced tumor senescence enhances the efficacy of immunotherapy by inhibiting AGT-PHB1 axis-mediated mitophagy in colorectal cancer.Autophagy · 2025Article
- m6A-mediated silencing of RNF41 by METTL3/YTHDC1 disrupts autophagy to drive intervertebral disc degeneration.Cell biology and toxicology · 2025Article
- Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.Journal of orthopaedic translation · 2025Review
- Review
- Targeted Inhibition of cGAS/STING signaling induced by aberrant R-Loops in the nucleus pulposus to alleviate cellular senescence and intervertebral disc degeneration.Journal of nanobiotechnology · 2025Article
- Article
- NJournal of orthopaedic translation · 2025Review
- Inhibiting the Histone Demethylase Kdm4a Restrains Cardiac Fibrosis After Myocardial Infarction by Promoting Autophagy in Premature Senescent Fibroblasts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From bone marrow mesenchymal stem cells to diseases: the crucial role of mStem cell research & therapy · 2025Review
- Exploring the methyl-verse: Dynamic interplay of epigenome and m6A epitranscriptome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- M6A RNA modification: focusing on non-small cell lung cancer progression, therapeutic strategies and challenges.Frontiers in oncology · 2025Review
- Cellular senescence: from homeostasis to pathological implications and therapeutic strategies.Frontiers in immunology · 2025Review
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe intervertebral disc (IVD) degeneration is the leading cause of low back pain, which accounts for a main cause of disability. N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs and is involved in various diseases and cellular processes by modulating mRNA fate. However, the critical role of m6A regulation in IVD degeneration remains unclear. Nucleus pulposus cell (NPC) senescence is critical for the progression of IVD degeneration. Here, we uncovered the role and explored the regulatory mechanism of m6A in NPC senescence during IVD degeneration.
methodsIdentification of NPC senescence during IVD degeneration was based on the analysis of tissue samples and the cellular model. ALKBH5 upregulation inducing cellular senescence was confirmed by functional experiments in vivo and in vitro. ChIP-qPCR and DNA-Pulldown were used to reveal increased ALKBH5 was regulated by KDM4A-mediated H3K9me3. Furthermore, Me-RIP-seq was performed to identify m6A hypomethylation of DNMT3B transcripts in senescent NPCs. Stability analysis showed that DNMT3B expression was enhanced for less YTHDF2 recognition and increased DNMT3B promoted NPC senescence and IVD degeneration via E4F1 methylation by in vivo and in vitro analyses.
resultsExpression of ALKBH5 is enhanced during IVD degeneration and NPC senescence, due to decreased KDM4A-mediated H3K9me3 modification. Functionally, ALKBH5 causes NPC senescence by demethylating DNMT3B transcripts and in turn promoting its expression via less YTHDF2 recognition and following degradation due to transcript hypomethylation in vitro and in vivo. Increased DNMT3B promotes the development of IVD degeneration and NPC senescence, mechanistically by methylating CpG islands of E4F1 at the promoter region and thus restraining its transcription and expression.
conclusionsCollectively, our findings reveal an epigenetic interplay mechanism in NPC senescence and IVD degeneration, presenting a critical pro-senescence role of ALKBH5 and m6A hypomethylation, highlighting the therapeutic potential of targeting the m6A/DNMT3B/E4F1 axis for treating IVD degeneration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.