Cellularity and Cartilage Matrix Increased in Hypertrophied Ligamentum Flavum Histopathological Analysis Focusing on the Mechanical Stress and Bone Morphogenetic Protein Signaling
Cellularity and Cartilage Matrix Increased in Hypertrophied Ligamentum Flavum Histopathological Analysis Focusing on the Mechanical Stress and Bone Morphogenetic Protein Signaling
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DOI：
10.1097/bsd.0b013e31820bb76e
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发表时间：
2012-04-01
影响因子：
--
通讯作者：
Nakamura, Hiroaki
中科院分区：
文献类型：
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作者：
Shafaq, Najibullah;Suzuki, Akinobu;Nakamura, Hiroaki
研究设计：组织病理学和免疫组织化学分析。目的：探讨肥厚黄韧带（LF）的组织学变化和骨形态发生蛋白（BMP）信号成分的表达，阐明机械应力对其的影响。背景资料摘要：肥厚的黄韧带改变是退行性腰椎管狭窄（DLCS）的主要因素，但其机制尚不清楚。 BMP 是调节许多细胞过程的生长因子，包括增殖、分化和细胞外基质合成。然而，一些研究调查了肥大的 LF 中 BMP 信号的表达。 方法：使用苏木精和伊红、弹性纤维吉森 (elastica van Gieson) 和甲苯胺蓝染色对总共 133 例 DLCS 患者的 LF 标本和 17 例腰椎间盘突出症患者的对照 LF 标本进行组织学分析。为了分析机械应力的影响，DLCS 标本分为 2 组：具有过度活动性的 DLCS 组和不具有过度活动性的 DLCS 组。通过磁共振图像测量LF厚度，并分析厚度与组织学数据之间的相关性。进行免疫组织化学分析以确认BMP信号成分的表达和定位。结果：肥大的LF中细胞数量和软骨基质面积显着增加，并且这些变化在过度活动的DLCS中比没有过度活动的DLCS更明显。软骨基质面积的细胞结构和百分比与LF厚度呈正线性相关。肥大的LF的许多细胞均表达BMP受体和BMP配体，其中一些细胞呈Sox9、CD105和Msx2阳性。过度活动的 DLCS 中每种 BMP 受体类型的免疫阳性细胞百分比显着高于无过度活动的 DLCS。 结论：较高的细胞结构和增加的软骨基质面积是 LF 肥大的重要变化。这些结果表明 BMP 信号传导和机械应力可能在肥大的 LF 中发挥作用。
Study Design: Histopathological and immunohistochemical analysis.Objective: To investigate the histological changes and expression of bone morphogenetic protein (BMP) signaling component in hypertrophied ligamentum flavum (LF), and to clarify the effect of mechanical stress on them.Summary of Background Data: Hypertrophic changes of the LF are a major factor in degenerative lumbar canal stenosis (DLCS), but their mechanism remains unclear. BMPs are growth factors that regulate many cellular processes including proliferation, differentiation, and extracellular matrix synthesis. However, a few studies have investigated the expressions of BMP signaling in the hypertrophied LF.Methods: A total of 133 LF specimens from patients with DLCS and 17 control LF specimens from patients with lumbar disc herniation were analyzed histologically using hematoxylin and eosin, elastica van Gieson, and toluidine blue staining. To analyze the influence of mechanical stress, the DLCS specimens were divided into 2 groups: DLCS with and DLCS without hypermobility groups. The LF thickness was measured by magnetic resonance image, and the correlations between the thickness and the histological data were analyzed. Immunohistochemical analyses were carried out to confirm the expressions and localizations of BMP signaling components.Results: The cell number and cartilage matrix area were significantly increased in the hypertrophied LF, and those changes were more obvious in DLCS with hypermobility than in DLCS without hypermobility. The cellularity and percentage of cartilage matrix area had positive linear correlations with the LF thickness. BMP receptors and BMP ligands were both expressed by many cells of the hypertrophied LF, and some of these cells were positive for Sox9, CD105, and Msx2. The percentage of immunopositive cells for each BMP receptor type was significantly higher in DLCS with hypermobility than in DLCS without hypermobility.Conclusions: Higher cellularity and increased cartilage matrix area are important changes in LF hypertrophy. These results suggest that BMP signaling and mechanical stress may play a role in the hypertrophied LF.