Decreased elastic fibers and increased proteoglycans in the ligamentum flavum of patients with lumbar spinal canal stenosis

Yabe, Yutaka; Hagiwara, Yoshihiro; Tsuchiya, Masahiro; Honda, Masahito; Hatori, Kouki; Sonofuchi, Kazuaki; Kanazawa, Kenji; Koide, Masashi; Sekiguchi, Takuya; Itaya, Nobuyuki; Itoi, Eiji

doi:10.1002/jor.23130

Cited by 33 publications

(35 citation statements)

References 49 publications

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“…The histology of many of these degenerative cyst contents has been described before and under various names. Changes seen in the histology of spinal stenosis include fibrosis, loss of elastic fibres, chondroid metaplasia, and deposition of calcium and proteoglycan matrix (similar to the myxoid material deposition described in the current cohort) . There are increased amounts of calcification in patients with lumbar spinal stenosis .…”

Section: Discussionsupporting

confidence: 66%

“…Changes seen in the histology of spinal stenosis include fibrosis, loss of elastic fibres, chondroid metaplasia, and deposition of calcium and proteoglycan matrix (similar to the myxoid material deposition described in the current cohort). [4][5][6] There are increased amounts of calcification in patients with lumbar spinal stenosis. 7-10 Calcium pyrophosphate dihydrate crystal deposition (pseudogout) has been described in the LF, 11 sometimes as the cause of hypertrophy of the LF.…”

Section: Discussionmentioning

confidence: 99%

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Histopathology of synovial cysts of the spine

et al. 2018

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Histology of 'synovial cysts' of the spine shows varied types of cyst; a large proportion are not synovial-lined cysts, but rather show pseudocystic degenerative changes of the ligamentum flavum, often associated with very characteristic finely granular calcifications and a foreign-body giant-cell reaction. This may have implications not only for understanding the pathogenesis of these lesions, but also for their varied responses to non-surgical interventions.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Histopathology of synovial cysts of the spine

et al. 2018

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“…It is mainly composed of elastic fibers, collagen fibers, reticular fibers and matrix. Yabe demonstrated through Elastic-Mason staining and alcian blue staining that degenerative LF possess reduced elastic fibers and elevated proteoglycans levels compared to normal LF [5,18]. Our study found a significant increase in positive H&E and VVG stained elastic tissue from the dorsal aspect to the dural aspect in LSS group.…”

Section: Discussionsupporting

confidence: 52%

The Expression of P16 and S100 Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum Hypertrophy

Author)

Kan

Liu

et al. 2019

Preprint

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Background: One of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and ﬁbrosis in the ligamentum ﬂavum (LF). P16 and S100 participate in scar formation and collagen development in wound healing and ﬁbrosis diseases. In this study, we investigate the association between P16 and S100 expression and the ﬁbrosis of the hypertrophic LF in LSS. Methods: The LF specimens were surgically obtained from thirty patients with single-segment LSS (SLSS) and 30 patients with double-segment LSS (DLSS). 30 patients with L4/5 lumbar disc herniation were included as control. The LF thickness was measured by axial T1-weighted Magnetic Resonance Imaging(MRI). The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (H&E) and Verhoff’s Van Gieson’s (VVG) stain, respectively. The localization of P16 and S100 within the LF tissue was determined by immunohistochemistry. Linear correlation tests between LF thickness, fibrosis, P16 and S100 expression was analyzed. Results: The Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The mean thickness in the DLSS group was 5.658mm (RT = 43.107), compared with 4.924 mm (RT=36.520) and 2.886 mm (RT=21.330), respectively in the SLSS and LDH groups. The amount of collagen deposition is significantly higher in the DLSS group compared with the SLSS and LDH groups (p < 0.05) as shown by the H&E staining. A higher level of elastic tissue was also seen in the DLSS group compared with the SLSS and LDH groups (p < 0.05) though VVG staining. There was a significant correlation between H&E mean rating and relative LF thickness in the DLSS group (r = 0.562; p = 0.010). The specimens in the DLSS group showed positive staining of P16. All the three groups were stained with S100 in the dorsal layer of the LF. Conclusions: Elastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. The expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with S100.

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“…Fig. IIID) was known to suppress elastin assembly 21 and it was reduced in the fibroblast relative to PA SMC conditioned media at baseline and with BMP4 or TGFβ1 stimulation. We then reduced decorin in PA SMC by siRNA and showed production of dense elastic fibers, (Suppl.…”

Section: Resultsmentioning

confidence: 97%

Codependence of Bone Morphogenetic Protein Receptor 2 and Transforming Growth Factor-β in Elastic Fiber Assembly and Its Perturbation in Pulmonary Arterial Hypertension

Tojais

Cao

Lai

et al. 2017

ATVB

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Objective We determined in patients with pulmonary arterial (PA) hypertension (PAH) whether in addition to increased production of elastase by PA smooth muscle cells (SMC) previously reported, PA elastic fibers are susceptible to degradation owing to their abnormal assembly. Approach and Results Fibrillin-1 and elastin are the major components of elastic fibers, and fibrillin-1 binds bone morphogenetic proteins (BMPs) and the large latent complex of transforming growth factor-β1 (TGFβ1). Thus, we considered whether BMPs like TGFβ1 contribute to elastic fiber assembly and whether this process is perturbed in PAH particularly when the BMP receptor, BMPR2, is mutant. We also assessed whether in mice with Bmpr2/1a compound heterozygosity, elastic fibers are susceptible to degradation. In PA SMC and adventitial fibroblasts (PAF), TGFβ1 increased elastin mRNA but the elevation in elastin protein, was dependent on BMPR2; TGFβ1 and BMP4, via BMPR2, increased extracellular accumulation of fibrillin-1. Both BMP4- and TGFβ1-stimulated elastic fiber assembly were impaired in idiopathic (I) PAH-PAF vs. control cells, particularly those with hereditary (H) PAH and a BMPR2 mutation. This was related to profound reductions in elastin and fibrillin-1 mRNA. Elastin protein was increased in IPAH PAF by TGFβ1 but only minimally so in BMPR2 mutant cells. Fibrillin-1 protein increased only modestly in IPAH or HPAH PAF stimulated with BMP4 or TGFβ1. In Bmpr2/1a heterozygote mice, reduced PA fibrillin-1 was associated with elastic fiber susceptibility to degradation and more severe pulmonary hypertension. Conclusion Disrupting BMPR2 impairs TGFβ1 and BMP4 mediated elastic fiber assembly and is of pathophysiologic significance in PAH.

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Decreased elastic fibers and increased proteoglycans in the ligamentum flavum of patients with lumbar spinal canal stenosis

Cited by 33 publications

References 49 publications

Histopathology of synovial cysts of the spine

Histopathology of synovial cysts of the spine

The Expression of P16 and S100 Associated with Elastin Degradation and Fibrosis of the Ligamentum Flavum Hypertrophy

Codependence of Bone Morphogenetic Protein Receptor 2 and Transforming Growth Factor-β in Elastic Fiber Assembly and Its Perturbation in Pulmonary Arterial Hypertension

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