Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Spine J. 2021 Jun;21(6):1010-1020. doi: 10.1016/j.spinee.2021.02.004. Epub 2021 Feb 10.
Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF.
To evaluate FGF9 expression and function in human LF with and without hypertrophy.
This study employed a basic research study design utilizing human LF tissue for histological analyses.
Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery.
LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF.
Histological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients' age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells.
The present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration.
The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.
黄韧带肥厚在腰椎管狭窄症（LSS）中起主导作用。先前的研究发现，兔黄韧带在机械应力下 FGF9 表达上调。然而，FGF9 在人黄韧带中的表达和功能尚不清楚。
评估有无肥厚的人黄韧带中 FGF9 的表达和功能。
本研究采用基础研究设计，用人黄韧带组织进行组织学分析。
在手术中从患有 LSS 的患者的肥厚黄韧带组织样本和患有腰椎间盘突出症或其他疾病的非肥厚（对照）黄韧带组织中获得。
通过免疫组织化学法对黄韧带标本进行 FGF9 和血管内皮生长因子 A（VEGF-A）的组织学分析。比较有无肥厚的黄韧带之间总细胞数和 FGF9 免疫阳性细胞及血管数。为了进行功能分析，使用人黄韧带的原代细胞培养物研究 FGF9 对细胞增殖和迁移的影响。
组织学研究显示，LSS 患者的黄韧带总细胞数明显高于对照组。免疫组织化学显示，LSS 患者的黄韧带中 FGF9 阳性细胞的百分比明显高于对照组，且与患者年龄呈正相关，与疾病无关。在肥厚黄韧带的纤维化区域中，FGF9 和 VEGF-A 双免疫阳性细胞常存在于血管内皮细胞和纤维母细胞中，LSS 患者的黄韧带中双阳性血管数明显高于对照组。人黄韧带的原代细胞培养显示，FGF9 促进黄韧带细胞的增殖和迁移。
本研究表明，FGF9 在人肥厚黄韧带中表达高度上调。FGF9 通过细胞增殖和迁移，在黄韧带肥厚的过程中可能发挥关键作用，这与机械应力有关。
本研究结果部分揭示了黄韧带肥厚的分子机制，并提示 FGF9 可能参与老年患者黄韧带退变的过程。
