Ossification of the ligamentum flavum: Diet and genetics

Mobbs, Ralph J.; Dvorak, Marcel F.

doi:10.1016/j.jocn.2006.01.010

Cited by 34 publications

(36 citation statements)

References 14 publications

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“…Currently, hypotheses about the contribution of mechanical/traumatic, 20,28,62 metabolic, 31,65 environmental, 35,37 chronic degenerative, 34,52 and biological/hereditary factors 24,69 have been proposed to explain the course of disease. Efforts directed at discovering the possible genetic components of OLF and OPLL have revealed certain human leukocyte antigen haplotypes 50 as well as genes such as COL6A1 to be associated with disease presentation.…”

Section: Discussionmentioning

confidence: 99%

Ossification of the ligamentum flavum in a Caucasian man

Sciubba

Gokaslan

et al. 2008

SPI

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Abnormal ossification of spinal ligaments is a well-known cause of myelopathy in East Asian populations, with ossification of the ligamentum flavum (OLF) and the posterior longitudinal ligament being the most prevalent. In Caucasian populations, OLF is rare, and there has been only 1 documented case of the disease affecting more than 5 spinal levels. In this report, the authors describe the clinical presentation, imaging characteristics, and management of the second published case of a Caucasian man with OLF affecting almost the entire thoracic spine. The literature is then reviewed with regard to OLF epidemiology, pathogenesis, presentation, and treatment.

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Section: Discussionmentioning

confidence: 99%

Ossification of the ligamentum flavum in a Caucasian man

Sciubba

Gokaslan

et al. 2008

SPI

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“…One paper indicates that over 70% of patients suffering from thoracic spinal stenosis have been diagnosed with TOLF [7]. It has been suggested that some related factors are associated with TOLF, such as genetic factors, basic metabolic elements, and mechanical effects [8,9]. However, the underlying etiology of TOLF is not well understood.…”

Section: Introductionmentioning

confidence: 99%

The involvement and possible mechanism of pro-inflammatory tumor necrosis factor alpha (TNF-α) in thoracic ossification of the ligamentum flavum

et al. 2017

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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 dosedependent 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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“…Thoracic OLF (TOLF) progresses insidiously over a long period of time, resulting in devastating spinal cord injury that invariably leads to serious myelopathy. Many factors contribute to OLF, including genetic background, dietary habits, metabolic abnormalities and mechanical stress (5–7). …”

Section: Introductionmentioning

confidence: 99%

Genetic differences in osteogenic differentiation potency in the thoracic ossification of the ligamentum flavum under cyclic mechanical stress

Ning

Chen

Fan

et al. 2016

International Journal of Molecular Medicine

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Mechanical stress and genetic factors play important roles in the occurrence of thoracic ossification of ligament flavum (TOLF), which can occur at one, two, or multiple levels of the spine. It is unclear whether single- and multiple-level TOLF differ in terms of osteogenic differentiation potency and osteogenesis-related gene expression under cyclic mechanical stress. This was addressed in the present study using patients with non-TOLF and single- and multiple-level TOLF (n=8 per group). Primary ligament cells were cultured and osteogenesis was induced by application of cyclic mechanical stress. Osteogenic differentiation was assessed by evaluating alkaline phosphatase (ALP) activity and the mRNA and protein expression of osteogenesis-related genes, including ALP, bone morphogenetic protein 2 (BMP2), Runt-related transcription factor-2 (Runx-2), osterix, osteopontin (OPN) and osteocalcin. The application of cyclic mechanical stress resulted in higher ALP activity in the multiple-level than in the single-level TOLF group, whereas no changes were observed in the non-TOLF group. The ALP, BMP2, OPN and osterix mRNA levels were higher in the multiple-level as compared to the single-level TOLF group, and the levels of all osteogenesis-related genes, apart from Runx2, were higher in the multiple-level as compared to the non-TOLF group. The osterix and ALP protein levels were higher in the multiple-level TOLF group than in the other 2 groups, and were increased with the longer duration of stress. These results highlight the differences in osteogenic differentiation potency between single- and multiple-level TOLF that may be related to the different pathogenesis and genetic background.

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Ossification of the ligamentum flavum: Diet and genetics

Cited by 34 publications

References 14 publications

Ossification of the ligamentum flavum in a Caucasian man

Ossification of the ligamentum flavum in a Caucasian man

The involvement and possible mechanism of pro-inflammatory tumor necrosis factor alpha (TNF-α) in thoracic ossification of the ligamentum flavum

Genetic differences in osteogenic differentiation potency in the thoracic ossification of the ligamentum flavum under cyclic mechanical stress

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