Department of Orthopaedic Surgery, School of Medicine, Fujita Health University, Aichi, Japan; Department of Spine and Spinal Cord, Fujita Health University, Aichi, Japan.
Department of Orthopaedic Surgery, School of Medicine, Fujita Health University, Aichi, Japan.
J Orthop Sci. 2021 Jul;26(4):560-565. doi: 10.1016/j.jos.2020.06.006. Epub 2020 Aug 1.
Although several causes of ligamentum flavum (LF) hypertrophy have been identified, the pathomechanisms underlying LF hypertrophy are not fully understood. Because collagen fibers are essential for the maintenance of LF tissues, characterization of the collagen composition of hypertrophied LF may help to elucidate the pathology of lumbar spinal canal stenosis (LCS). This study aimed to determine the association between the collagen composition and LF hypertrophy.
LF tissues were collected from 23 patients who underwent spinal decompression surgery for lumbar disorders. The cross-sectional area of LF was measured using the axial images of lumbar MRI. The expression of each collagen in human surgical samples was evaluated by real-time RT-PCR and immunohistochemical analysis. To investigate the impact of inflammatory cytokines on the expression of each collagen, we treated primary human LF cells with TNF-α or IL-1β.
Real-time RT-PCR analysis and immunohistochemistry showed that of the 28 types of collagen, collagen type I, III, V, VI, VIII were highly expressed regardless of LF hypertrophy. In addition, we found the moderate correlation between the cross-sectional area of LF and the mRNA expression level of collagen type I, III, and VI. In vitro analysis showed that the mRNA expression of collagen type I, III, V, VI, and VIII was up-regulated by treatment with TNF-α and with IL-1β.
Our results suggested that collagen type I, III, V, VI, and VIII were the main components of the LF extracellular matrix and that collagen type I, III, and VI may serve as useful markers of LF hypertrophy. These findings may contribute to the future development of diagnostic and treatment modalities for LF hypertrophy and even LCS.
尽管已经确定了几种黄韧带(LF)肥厚的原因,但 LF 肥厚的发病机制尚不完全清楚。由于胶原纤维对于 LF 组织的维持至关重要,因此对肥厚 LF 的胶原组成进行特征分析可能有助于阐明腰椎管狭窄症(LCS)的病理学。本研究旨在确定胶原组成与 LF 肥厚之间的关联。
从 23 例因腰椎疾病接受脊柱减压手术的患者中收集 LF 组织。使用腰椎 MRI 的轴向图像测量 LF 的横截面积。通过实时 RT-PCR 和免疫组织化学分析评估人手术样本中每种胶原的表达。为了研究炎症细胞因子对每种胶原表达的影响,我们用 TNF-α或 IL-1β处理原代人 LF 细胞。
实时 RT-PCR 分析和免疫组织化学显示,在 28 种胶原中,I、III、V、VI、VIII 型胶原无论 LF 是否肥厚均高表达。此外,我们还发现 LF 横截面积与 I、III、VI 型胶原的 mRNA 表达水平之间存在中度相关性。体外分析显示,TNF-α和 IL-1β处理可上调 I、III、V、VI 和 VIII 型胶原的 mRNA 表达。
我们的结果表明,I、III、V、VI 和 VIII 型胶原是 LF 细胞外基质的主要成分,I、III 和 VI 型胶原可能作为 LF 肥厚的有用标志物。这些发现可能有助于未来开发 LF 肥厚甚至 LCS 的诊断和治疗方法。