Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression

Löhr, Mario; Hampl, Jürgen A.; Lee, Jin Yul; Ernestus, Ralf‐Ingo; Deckert, Martina; Stenzel, Werner

doi:10.1007/s00701-010-0839-7

Cited by 58 publications

(65 citation statements)

References 34 publications

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“…In the recent years, several cytokines and growth factors have been studied in patients with LSCS. TGF-β has been documented to play a significant part for the hypertrophy of LF [18]. Zhang and coworkers reported that the increased expression of platelet-derived growth factor-BB was observed in the hypertrophic lumbar LF [19].…”

Section: Discussionmentioning

confidence: 99%

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

Honsawek

Poonpukdee

Chalermpanpipat

et al. 2013

International Orthopaedics (SICOT)

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Purpose A prospective study was undertaken to investigate basic fibroblast growth factor (bFGF) expression in hypertrophic ligamentum flavum (LF) from patients with lumbar spinal canal stenosis (LSCS) and to determine whether there was a correlation of bFGF expression with LF thickness. Methods Twenty patients with lumbar spinal canal stenosis were enrolled in this study. bFGF mRNA and protein expressions in LF were analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. The thickness of LF was measured by axial T1-weighted magnetic resonance imaging. Results Expression of bFGF was substantially higher in the hypertrophic LF group than in the control group (P<0.001) as quantified by quantitative real-time PCR. In immunohistochemical study, bFGF was positively stained on the fibroblasts within hypertrophic LF compared to nonpathologic LF of controls. Subsequent ELISA analysis revealed that bFGF concentration in the hypertrophic LF group was remarkably higher than that in the control group (P=0.003). The thickness of LF in the hypertrophic LF was significantly greater than that in the control group (P<0.001). LSCS patients with greater severity of LF hypertrophy had significantly higher bFGF levels in the LF tissues (P<0.001). Furthermore, the bFGF concentration exhibited a positive correlation with the LF thickness (r=0.974, P<0.001). Conclusions These findings suggest that the increased expression of bFGF is associated with the hypertrophy of ligamentum flavum in patients with LSCS.

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Section: Discussionmentioning

confidence: 99%

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

Honsawek

Poonpukdee

Chalermpanpipat

et al. 2013

International Orthopaedics (SICOT)

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“…In a study conducted by Park et al, which compared the lumbar spinal stenosis and lumbar disc hernias, the levels of the TGF-β1 were found significantly higher in the patients with lumbar spinal stenosis (24). In another experimental study, it was revealed that the ligamentum flavum hypertrophy is associated with TGF-β1 expression (25). In our study too, the TGF-β1 concentrations were found significantly higher among the patients with lumbar spinal stenosis in comparison to other two groups, which is consistent with the existing literature.…”

Section: Discussionmentioning

confidence: 95%

Relationship of ligamentum flavum hypertrophy in lumbar spinal stenosis with transforming growth factor β-1

Gokpinar¹,

Ozlece²,

Akyüz³

et al. 2017

Journal of Contemporary Medicine

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“…Elastin-Derived Peptides Induce Ligamentum Flavum Inflammation  number, when in contrast with nonhypertrophied specimens [2,12]. However, the actual amount of EDPs existing in human LF tissue has to be determined.…”

Section: Discussionmentioning

confidence: 96%

“…LF cells subjected to mechanical stress in vitro showed a notable increase in TGF-β1 and collagen gene expression [22]. However, recent histological examination of hypertrophied LF by Lohr et al [12] showed that macrophages and endothelial cells were major cellular sources of TGF-β in advanced hypertrophy of LF and may perpetuate further hypertrophy. These conflicting findings raise the question of whether EDPs directly enhance TGF-β1 production leading to collagen deposition in human LF cells.…”

Section: Discussionmentioning

confidence: 97%

Elastin-Derived Peptides Induce Inflammatory Responses through the Activation of NF-κB in Human Ligamentum Flavum Cells

Chao¹,

Yang²,

Sun

et al. 2012

Connective Tissue Research

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The formation of fibrotic tissue in the ligamentum flavum (LF) is usually preceded by breakdown of elastic fibers. Elastin-derived peptides (EDPs) from breakdown of elastic fibers display a wide range of biological activities in a variety of cells, but there is minimal information regarding the involvement in the processes of LF hypertrophy. The aim of this study is to elucidate the effects of EDPs on cultured human LF cells and to investigate their molecular and biochemical mechanisms. Human LF cells were obtained from 18 patients who underwent lumbar spine surgery. After treatment with different concentrations of EDPs with or without specific inhibitors in culture medium, the viability and proliferation of LF cells, genes expression, and the signaling pathways were evaluated and analyzed. It was found that 50 μg/ml EDPs significantly increased cell proliferation and synthesis of prostaglandin E(2). The gene expression and protein production of proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, and IL-6, were also upregulated. The levels of p-ERK (extracellular signal-regulated kinase) and NF-κB increased immediately following EDP treatment and sustained up to 90 min. It was also found that NF-κB inhibitor, but not ERK1/2 inhibitor, attenuated EDP-dependent induction of IL-1α, IL-1β, and IL-6 expression, indicating that NF-κB pathways are required for EDP-induced IL-1α, IL-1β, and IL-6 gene expression in human LF cells. The results of this in vitro experiment suggest that EDPs do induce inflammatory responses in human LF cells and plays the key role in the development of LF hypertrophy.

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Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression

Abstract: Macrophages were identified as a major cellular source of TGF-β in advanced HLF and may perpetuate further hypertrophy. This finding suggests that modulating the immune response locally or systemically could prove to be effective for impeding the disease progress.

Cited by 58 publications

References 34 publications

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with increased bFGF expression

Relationship of ligamentum flavum hypertrophy in lumbar spinal stenosis with transforming growth factor β-1

Elastin-Derived Peptides Induce Inflammatory Responses through the Activation of NF-κB in Human Ligamentum Flavum Cells

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