ArticleEuropean journal of human genetics : EJHG2017
Two novel BMP-2 variants identified in patients with thoracic ossification of the ligamentum flavum.
Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Integrative Transcriptomic Profiling Delineates LTBP4-Driven Fibroblast Reprogramming Across the Ossification Continuum of the Ligamentum Flavum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Biological mechanisms underlying the ossification of ligamentum flavum and potential therapeutic targets derived from current research.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2025Review
- Potential Influence of Sagittal Parameters in the Pathogenesis of Patients With the Thoracic Ossification of the Ligamentum Flavum.Orthopaedic surgery · 2025Article
- METTL3 regulated by histone lactylation promotes ossification of the ligamentum flavum by enhancing the m6A methylation of BMP2.Molecular medicine (Cambridge, Mass.) · 2025Article
- Identification of Risk Factors for Primary Osteoporosis: The Role of Cervical Ligament Ossification.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- M1 macrophage-derived oncostatin M induces osteogenic differentiation of ligamentum flavum cells through the JAK2/STAT3 pathway.JOR spine · 2024Article
- Pathogenesis of thoracic ossification of the ligamentum flavum.Frontiers in pharmacology · 2024Review
- LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.Journal of cellular and molecular medicine · 2022Article
- Disruption of the mouse Bmal1 locus promotes heterotopic ossification with aging via TGF-beta/BMP signaling.Journal of bone and mineral metabolism · 2022Article
- Article
- Investigation of the biomarkers involved in ectopic ossification: The shared mechanism in ossification of the spinal ligament.Frontiers in genetics · 2022Article
- Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review.Frontiers in genetics · 2022Review
- Association analysis and functional study of COL6A1 single nucleotide polymorphisms in thoracic ossification of the ligamentum flavum in the Chinese Han population.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2021Article
- Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. a Single-Centre Study.Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2021Article
- Cyclic stretch promotes the ossification of ligamentum flavum by modulating the Indian hedgehog signaling pathway.Molecular medicine reports · 2020Article
- Genome-wide DNA methylation profile analysis in thoracic ossification of the ligamentum flavum.Journal of cellular and molecular medicine · 2020Article
- Heterotopic ossification of tendon and ligament.Journal of cellular and molecular medicine · 2020Review
- Regulatory effect of miR-421 on humeral fracture and heterotopic ossification in elderly patients.Experimental and therapeutic medicine · 2019Article
- Angiopoietin-2 promotes osteogenic differentiation of thoracic ligamentum flavum cells via modulating the Notch signaling pathway.PloS one · 2018Article
- MiR-490-3p inhibits osteogenic differentiation in thoracic ligamentum flavum cells by targeting FOXO1.International journal of biological sciences · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thoracic ossification of the ligamentum flavum (TOLF)is a common cause of thoracic spinal canal stenosis and has been reported almost exclusively in East Asian countries. In this study, we established a relationship between bone morphogenic protein 2 (BMP-2) and TOLF. We divided patients into two groups according to severity of ossification and identified susceptible loci through exome sequencing. We identified 39 novel likely pathogenic variants in 29 genes in the transforming growth factor-beta (TGF-β) superfamily or TGF-β/BMPs signaling pathway, including two missense variants in BMP-2 (NM_001200.3) exon region, c.460C>G:p.(R154G) and c.584G>T:p.(R195M). Further Sanger sequencing and genotyping suggested the variants were only found in patients with long regional OLF. Bioinformatic assays predicted the two BMP-2 variants to cause significant alterations to gene and protein expression. Functional assays showed upregulation of BMP-2 expression, increased osteogenic marker expression, and enhanced osteogenic differentiation. Collectively, these results suggest a genetic contribution to the pathogenesis of TOLF, particularly in patients with long segment disease, and that nucleotide substitutions associated with increased BMP-2 expression may be involved in TOLF pathogenesis.
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