Degeneration and Ossification of the Yellow Ligament in Unstable Spine

Nakamura, Takafumi; Hashimoto, Noburo; Maeda, Yuichi; Ikeda, Takashi; Nakagawa, Hiroaki; Takagi, Katsumasa

doi:10.1097/00002517-199012000-00002

Cited by 41 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, even different TOLF cells exhibited different levels of mineralization in response to leptin treatment in our experiments. It is conceivable that osteogenic commitment of the cells in the ossification process of TOLF and the metaplasia of TOLF cells into osteogenic cells have already occurred in TOLF, which is consistent with other studies of OLF pathogenesis (19,48). Further studies are warranted to investigate the molecular mechanism underlying osteogenic commitment of TOLF cells and molecular events involved in the initiation of TOLF.…”

Section: Discussionsupporting

confidence: 86%

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Fan

Chen

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Obesity is a risk factor for thoracic ossification of ligament flavum (TOLF) that is characterized by ectopic bone formation in the spinal ligaments. Hyperleptinemia is a common feature of obese people, and leptin, an adipocyte-derived cytokine with proliferative and osteogenic effects in several cell types, is believed to be an important factor in the pathogenesis of TOLF. However, how leptin might stimulate cell osteogenic differentiation in TOLF is not totally understood. We reported here that leptin-induced osteogenic effect in TOLF cells is associated with activation of signaling molecules STAT3, JNK, and ERK1/2 but not p38. Blocking STAT3 phosphorylation with a selective inhibitor, AG490, significantly abolished leptin-induced osteogenic differentiation of TOLF cells, whereas blocking ERK1/2 and JNK phosphorylation with their selective inhibitors PD98059 and SP600125, respectively, had only marginal effects. In addition, we showed that STAT3 interacted with Runt-related transcription factor 2 (Runx2) in the nucleus, and STAT3, Runx2, and steroid receptor coactivator steroid receptor coactivator-1 were components of the transcription complex recruited on Runx2 target gene promoters in response to leptin treatment. Our experiments identified STAT3, Runx2, and steroid receptor coactivator-1 as critical molecules in mediating leptin-stimulated cell osteogenesis in TOLF. Ossification of ligament flavum (OLF)3 of the spine is characterized by a heterotopic bone formation in the ligament flavum that is normally composed of fibrous tissues (1). Ossification could enlarge the spinal canal and compresses the spinal cord, resulting in serious neurological damages. Epidemiology has shown that high incidence rate of OLF occurs in thoracic spine (2). It has been documented that obesity represents a risk factor for thoracic ossification of ligament flavum (TOLF), particularly in Asian people (3). Indeed, hereditary obese rats, Zucker fatty (fa/fa) rats, are prone to OLF (4). A common feature of obese people is hyperleptinemia (5). Leptin, an adipocyte-derived cytokine, can stimulate the proliferation and osteogenic differentiation of various cell lines, such as the embryonic cell line C3H10T1/2, human NHOst cells, and human osteoblastic cells (6, 7). However, the molecular mechanism underlying the osteogenic effect of leptin in TOLF is not totally understood.Leptin exerts its biological activity through binding to its receptors, which belong to cytokine receptor superfamily. Different leptin receptor isoforms exist, including a long form (ObRb) and a short form (ObRa) (8). In vitro and in vivo studies have shown that leptin activates cytokine-like signal transduction via the long form receptor. Upon leptin stimulation, intracellular Janus tyrosine kinases are activated via transphosphorylation and phosphorylate tyrosine residues on the long form leptin receptor and on signal transducers and activators of transcription (STAT) proteins (9). Phosphorylated STAT proteins dimerize and translocate to the nucleus to activate ge...

show abstract

Section: Discussionsupporting

confidence: 86%

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Fan

Chen

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Histological research data have shown that an increased LF thickness is associated with an increase in fibrosis (i.e., an increase in collagen fiber content) and a decrease in elastic fibers [13161718]. Epidemiologically, mechanical stress attributable to spinal instability may initiate LF hypertrophy [16253031]. However, the mechanism inciting lumbar mechanical stress remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis

et al. 2016

View full text Add to dashboard Cite

Study DesignCross-sectional study.PurposeTo investigate the relationship between ligamentum flavum (LF) thickening and lumbar segmental instability and disc degeneration and facet joint osteoarthritis.Overview of LiteraturePosterior spinal structures, including LF thickness, play a major role in lumbar spinal canal stenosis pathogenesis. The cause of LF thickening is multifactorial and includes activity level, age, and mechanical stress. LF thickening pathogenesis is unknown.MethodsWe examined 419 patients who underwent computed tomography (CT) myelography and magnetic resonance imaging after complaints of clinical symptoms. To investigate LF hypertrophy, 57 patients whose lumbar vertebra had normal disc heights at L4–5 were selected to exclude LF buckling as a hypertrophy component. LF thickness, disc space widening angulation in flexion, segmental angulation, presence of a vacuum phenomenon, and lumbar lordosis at T12–S1 were investigated. Disc and facet degeneration were also evaluated. Facet joint orientation was measured via an axial CT scan.ResultsThe mean LF thickness in all patients was 4.4±1.0 mm at L4–5. There was a significant correlation between LF thickness and disc degeneration; LF thickness significantly increased with severe disc degeneration and facet joint osteoarthritis. There was a tendency toward increased LF thickness in more sagittalized facet joints than in coronalized facet joints. Logistic regression analysis showed that LF thickening was influenced by segmental angulation and facet joint osteoarthritis. Patient age was associated with LF thickening.ConclusionsLF hypertrophy development was associated with segmental instability and severe disc degeneration, severe facet joint osteoarthritis, and a sagittalized facet joint orientation.

show abstract

“…In this study, we confirmed that the occurrence of RNRs in central LSS show stronger association with LF hypertrophy than the other structure in the spinal canal. Multiple studies supported that LF hypertrophy is a major pathogenic factor of central LSS4,12,22), and that LF hypertrophy has close relationship with mechanical stress2,7,9,10,16). Furthermore, repetitive (longer duration) wide motion (wide segmental angulation) in maximal stenotic level could be considered as high mechanical stress that may lead to development of LF hypertrophy7).…”

Section: Discussionmentioning

confidence: 99%

Radiological Significance of Ligamentum Flavum Hypertrophy in the Occurrence of Redundant Nerve Roots of Central Lumbar Spinal Stenosis

Hur

Kwon

et al. 2012

J Korean Neurosurg Soc

View full text Add to dashboard Cite

ObjectiveThere were previous reports of redundant nerve roots (RNRs) focused on their clinical significance and pathogenesis. In this study, we investigated the significant radiologic findings that correlate with RNRs occurrence. These relations would provide an advanced clue for clinical significance and pathogenesis of RNRs.MethodsRetrospective research was performed with data from 126 patients who underwent surgery for central lumbar spinal stenosis (LSS). Finally, 106 patients with common denominators (inter-observer accuracy : 84%) were included on this study. We divided the patients into two groups by MRI, patients with RNRs and those with no RNRs (NRNRs). Comparative analyses were performed with clinical and radiologic parameters.ResultsRNRs were found in 45 patients (42%) with central LSS. There were no statistically significant differences between the two groups in severity of symptoms. On the other hand, we found statistically significant differences in duration of symptom and number of level included (p<0.05). In the maximal stenotic level, ligamentum flavum (LF) thickness, LF cross-sectional area (CSA), dural sac CSA, and segmental angulation are significantly different in RNRs group compared to NRNRs group (p<0.05).ConclusionRNRs patients showed clinically longer duration of symptoms and multiple levels included. We also confirmed that wide segmental angulation and LF hypertrophy play a major role of the development of RNRs in central LSS. Together, our results suggest that wide motion in long period contribute to LF hypertrophy, and it might be the key factor of RNRs formation in central LSS.

show abstract

Degeneration and Ossification of the Yellow Ligament in Unstable Spine

Cited by 41 publications

References 0 publications

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Mechanistic Roles of Leptin in Osteogenic Stimulation in Thoracic Ligament Flavum Cells

Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis

Radiological Significance of Ligamentum Flavum Hypertrophy in the Occurrence of Redundant Nerve Roots of Central Lumbar Spinal Stenosis

Contact Info

Product

Resources

About