ArticlePloS one2017
The involvement and possible mechanism of pro-inflammatory tumor necrosis factor alpha (TNF-α) in thoracic ossification of the ligamentum flavum.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions.Frontiers in genetics · 2021Pooled it
- 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
- Cellular and molecular mechanisms underlying obesity in degenerative spine and joint diseases.Bone research · 2024Review
- Revealing the novel metabolism-related genes in the ossification of the ligamentum flavum based on whole transcriptomic data.JOR spine · 2024Article
- The involvement of epidural fat in ossification of the ligamentum flavum: From the perspective of exosomal proteome.Heliyon · 2024Article
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- Single-cell RNA sequencing uncovers cellular heterogeneity and the progression of heterotopic ossification of the elbow.Frontiers in pharmacology · 2024Article
- Pathogenesis of thoracic ossification of the ligamentum flavum.Frontiers in pharmacology · 2024Review
- Unearths IFNB1 immune infiltrates in SOP-related ossification of ligamentum flavum pathogenesis.Heliyon · 2023Article
- Clinical progression of ossification of the ligamentum flavum in thoracic spine: a 10- to 11-year follow-up study.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 · 2023Article
- PTGR1 is involved in cell proliferation in thoracic ossification of the ligamentum flavum.PloS one · 2023Article
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- LGR5 regulates osteogenic differentiation of human thoracic ligamentum flavum cells by Wnt signalling pathway.Journal of cellular and molecular medicine · 2022Article
- Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis.Frontiers in endocrinology · 2022Article
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- High Systemic Immune-Inflammation Index and Body Mass Index Are Independent Risk Factors of the Thoracic Ossification of the Ligamentum Flavum.Mediators of inflammation · 2022Article
- 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
- Thoracic ligamentum flavum ossification: a rare cause of spinal cord injury without tomographic evidence of trauma in a Caucasian patient. Case report and literature review.Spinal cord series and cases · 2021Review
- Relationship between Scheuermann disease and symptomatic thoracic spinal stenosis: A retrospective study.Acta orthopaedica et traumatologica turcica · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thoracic ossification of the ligamentum flavum (TOLF) is characterized by ectopic bone formation in the ligamentum flavum and is considered to be a leading cause of thoracic spinal canal stenosis and myelopathy. However, the underlying etiology is not well understood. An iTRAQ proteomics was used to reveal the involvement of inflammation factors in TOLF. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of many human diseases. Protein profiling analysis showed that the protein level of TNF-α increased in the ossified ligamentum flavum of TOLF, which was confirmed by western blot. The effects of TNF-α on primary ligamentum flavum cells was examined. Cell proliferation assay demonstrated that primary cells from the ossified ligamentum flavum of TOLF grew faster than the control. Flow cytometry assay indicated that the proportions of cells in S phase of cell cycle of primary cells increased after TNF-α stimulation. To address the effect of TNF-α on gene expression, primary cells were derived from ligamentum flavum of TOLF patients. Culture cells were stimulated by TNF-α. RNA was isolated and analyzed by quantitative RT-PCR. G1/S-specific proteins cyclin D1 and c-Myc were upregulated after TNF-α stimulation. On the other hand, osteoblast differentiation related genes such as Bmp2 and Osterix (Osx) were upregulated in the presence of TNF-α. TNF-α activated Osx expression in a dose-dependent manner. Interestingly, a specific mitogen-activated protein kinase ERK inhibitor U0126, but not JNK kinase inhibitor SP600125, abrogated TNF-α activation of Osx expression. This suggests that TNF-α activates Osx expression through the mitogen-activated protein kinase ERK pathway. Taken together, we provide the evidence to support that TNF-α involves in TOLF probably through regulating cell proliferation via cyclin D1 and c-Myc, and promoting osteoblast differentiation via Osx.
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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.