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腹侧和背侧黄韧带层之间细胞外基质拓扑结构、纤维排列、机械刚度和细胞组成的差异:对肥厚发病机制的见解。

Variations in ECM Topography, Fiber Alignment, Mechanical Stiffness, and Cellular Composition Between Ventral and Dorsal Ligamentum Flavum Layers: Insights Into Hypertrophy Pathogenesis.

作者信息

Tu Ting-Yuan, Hsu Yu-Chia, Yang Chia-En, Shyong Yan-Jye, Kuo Cheng-Hsiang, Liu Yuan-Fu, Shih Shu-Shien, Lin Cheng-Li

机构信息

Department of Biomedical Engineering, College of Engineering National Cheng Kung University Tainan Taiwan.

Medical Device Innovation Center National Cheng Kung University Tainan Taiwan.

出版信息

JOR Spine. 2025 Jan 30;8(1):e70033. doi: 10.1002/jsp2.70033. eCollection 2025 Mar.

Abstract

BACKGROUND

Previous studies have suggested that changes in the composition of the extracellular matrix (ECM) play a significant role in the development of ligamentum flavum hypertrophy (LFH) and the histological differences between the ventral and dorsal layers of the hypertrophied ligamentum flavum. Although LFH is associated with increased fibrosis in the dorsal layer, comprehensive research exploring the characteristics of the ECM and its mechanical properties in both regions is limited. Furthermore, the distribution of fibrosis-associated myofibroblasts within LFH remains poorly understood. This study aimed to bridge the existing knowledge gap concerning the intricate relationships between ECM characteristics, mechanical properties, and myofibroblast expression in LFH.

METHODS

Histological staining, scanning electron microscopy, and atomic force microscopy were used to analyze the components, alignment, and mechanical properties of the ECM. Immunostaining and western blot analyses were performed to assess the distribution of myofibroblasts in LF tissues.

RESULTS

There were notable differences between the dorsal and ventral layers of the hypertrophic ligamentum flavum. Specifically, the dorsal layer exhibited higher collagen content and disorganized fibrous alignment, resulting in reduced stiffness. Immunohistochemistry analysis revealed a significantly greater presence of α-smooth muscle actin (αSMA)-stained cells, a marker for myofibroblasts, in the dorsal layer.

CONCLUSIONS

This study offers comprehensive insights into LFH by elucidating the distinctive ECM characteristics, mechanical properties, and cellular composition disparities between the ventral and dorsal layers. These findings significantly enhance our understanding of the pathogenesis of LFH and may inform future research and therapeutic strategies.

摘要

背景

先前的研究表明,细胞外基质(ECM)组成的变化在黄韧带肥厚(LFH)的发展以及肥厚黄韧带腹侧和背侧层之间的组织学差异中起重要作用。尽管LFH与背侧层纤维化增加有关,但探索这两个区域ECM特征及其力学性能的综合研究有限。此外,LFH内纤维化相关肌成纤维细胞的分布仍知之甚少。本研究旨在填补关于LFH中ECM特征、力学性能和肌成纤维细胞表达之间复杂关系的现有知识空白。

方法

采用组织学染色、扫描电子显微镜和原子力显微镜分析ECM的成分、排列和力学性能。进行免疫染色和蛋白质印迹分析以评估肌成纤维细胞在LF组织中的分布。

结果

肥厚黄韧带的背侧层和腹侧层之间存在显著差异。具体而言,背侧层表现出更高的胶原蛋白含量和纤维排列紊乱,导致硬度降低。免疫组织化学分析显示,背侧层中α平滑肌肌动蛋白(αSMA)染色细胞(肌成纤维细胞的标志物)的存在明显更多。

结论

本研究通过阐明腹侧和背侧层之间独特的ECM特征、力学性能和细胞组成差异,为LFH提供了全面的见解。这些发现显著增强了我们对LFH发病机制的理解,并可能为未来的研究和治疗策略提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5633/11780719/3b05db11a126/JSP2-8-e70033-g001.jpg

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