Abstract

BackgroundOne of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). However, the biochemical factors that cause these histologic changes is unclear. 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.MethodsThe LF specimens were surgically obtained from 30 patients with single-segment LSS (SLSS), 30 patients with double-segment LSS (DLSS) and 30 patients with L4/5 lumbar disc herniation (LDH). The LF thickness was measured by axial T1-weighted MRI. The extent of LF elastin degradation and fibrosis were graded based on hematoxylin-eosin (HE) and Verhoff’s Van Gieson’s (VVG) stain, respectively. The localization of P16 and S100 was determined by immunohistochemistry.ResultsThe Absolute and relative LF thickness were greater in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The elastic tissue from the dorsal aspect to the dural aspect in SLSS and DLSS groups was significantly increased. The amount of collagen deposition and elastic tissue is significantly higher in the DLSS group compared with the SLSS and LDH groups (p < 0.05). The specimens in the DLSS group showed positive staining of P16, especially in the dorsal layer. Almost all samples in the SLSS group were partially positive for P16. The LDH group showed negative staining of P16 in both the dural and dorsal layers. All the three groups were stained with S100 in the dorsal layer of the LF. On the contrary, S100 staining was absent in the dural layer of the LF in the three groups.ConclusionsElastin degradation and fibrosis of the LF in the DLSS patients is more severe compared with the SLSS and LDH patients. Increased expression of P16 associated with LF fibrosis and thickness, suggested that the expression of P16 may related to LF hypertrophy in the patients who suffer with LSS. LF hypertrophy process may not be associated with high expression of S100.

Highlights

  • One of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF)

  • The purpose of the study is to explore: (1) the histological difference of LF hypertrophy in three groups; (2) Correlation between the degree of LF hypertrophy assess through MRI and hematoxylin-eosin (HE) and Verhoff’s Van Gieson’s (VVG) staining; (3) whether P16 and S100 are associated with LF hypertrophy; (4) Whether segment LSS (SLSS) and double-segment LSS (DLSS) differ in P16 and S100 expression

  • There was no significant difference between the dorsal aspect and the dural aspect in the lumbar disc herniation (LDH) group in both HE and VVG staining

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Summary

Introduction

One of the characteristics of lumbar spinal stenosis (LSS) is elastin degradation and fibrosis in the ligamentum flavum (LF). Lumbar spinal stenosis (LSS) is a common disease, usually causing lower back pain and limited walking. It was shown in recent study that applying consecutive mechanical flexionextension stress to mouse LF led to macrophage infiltration in the progression of LF hypertrophy. Both in vivo and in vitro studies have demonstrated that mechanical stress can be a potential stimulus factor in LF hypertrophy, the mechanism of hypertrophic LF progression still remains unknown [8]

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