ArticleMolecular medicine (Cambridge, Mass.)2025
METTL3 regulated by histone lactylation promotes ossification of the ligamentum flavum by enhancing the m6A methylation of BMP2.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- METTL3-mediated m6A methylation to promote mandibular condyle fracture repair via TGF-β/Smad signaling pathway.Scientific reports · 2026Article
- Lactylation in tissue fibrosis: epigenetic mechanisms, metabolic crosstalk, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Targeting lactylation in a novel metabolic-epigenetic-inflammatory axis mitigates inflammation and promotes healing following corneal injury.Journal of translational medicine · 2026Article
- Hypoxic BMSCs accelerate femur fracture healing via the METTL3/SLC2A3 m6A-glycolysis axis.Journal of translational medicine · 2025Article
- Lactylation Dynamics and Its Regulatory Roles in Orthopedic Pathologies: A Research Update.Journal of proteome research · 2025Review
- Targeting Lactylation: From Metabolic Reprogramming to Precision Therapeutics in Liver Diseases.Biomolecules · 2025Review
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Authors and funding
4 authors.
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Abstract
Ossification of the ligamentum flavum (OLF) is characterized by ligamentum flavum thickening and subsequent thoracic canal stenosis. Emerging evidence has demonstrated the involvement of N6-methyladenosine (m6A) methylation in OLF pathogenesis. This study investigates the regulatory role of METTL3-mediated m6A methylation of BMP2 in OLF progression. Clinical ligamentum flavum tissues were analyzed for m6A levels using dot blot analysis. Osteogenic differentiation was assessed through quantitative real-time PCR (qPCR), alkaline phosphatase staining, alizarin red S staining, and western blot analysis. Mechanistic insights were obtained through methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays. The regulatory role of histone lactylation on METTL3 expression was examined using LDHA knockdown, sodium lactate (Nala) treatment, and 2-deoxy-D-glucose (2-DG) administration in OLF cells. Our findings revealed significant upregulation of METTL3 expression and m6A levels in OLF patients. METTL3 was shown to enhance osteogenic differentiation and m6A methylation of BMP2, which was specifically recognized by IGF2BP1. Furthermore, increased histone lactylation was observed in OLF patients, with enrichment in the METTL3 promoter region facilitating its transcriptional activation. LDHA knockdown-mediated inhibition of endogenous lactylation suppressed osteogenic differentiation, a phenotype that was rescued by METTL3 overexpression. In conclusion, this study elucidates that histone lactylation-mediated upregulation of METTL3 promotes OLF progression through IGF2BP1-dependent m6A methylation of BMP2, providing novel insights into potential therapeutic strategies for OLF management.
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