Ham Chang Hwa, Kim Yiseul, Kwon Woo-Keun, Sun Woong, Kim Joo Han, Kim Hyun Jung, Moon Hong Joo
Department of Biomedical Sciences, College of Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; Department of Neurosurgery, Korea University Guro Hospital, Seoul 08308, Republic of Korea.
Department of Biomedical Sciences, College of Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea; Department of Anatomy, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Spine J. 2025 Jun;25(6):1263-1275. doi: 10.1016/j.spinee.2024.12.001. Epub 2024 Dec 7.
The ligamentum flavum (LF) is a crucial structure in maintaining spinal stability; however, hypertrophy of the LF is a significant contributor to lumbar spinal canal stenosis (LSCS). The mechanisms linking LF hypertrophy to the exacerbation of LSCS remain incompletely understood.
This study aimed to investigate the cellular proportions and signaling pathways observed in the hypertrophied LF.
LF tissues were obtained from 3 patients undergoing lumbar decompressive surgery. These patients had been diagnosed with LSCS prior to surgery and had an LF thickness exceeding 3.5 mm.
Single-cell RNA sequencing was performed following LF tissue dissociation, and data were processed for quality control, dimensional reduction, and clustering. Differential gene expression and gene ontology analyses revealed key molecular pathways driving LF hypertrophy. Cell-cell communication analysis was analyzed to elucidate interactions among various cell types within the LF tissues.
Fibroblasts accounted for 75% of the total cells, followed by endothelial cells, T cells, macrophages, and B cells. Among heterogeneous types of fibroblasts, we identified that a subset of fibroblasts trans-differentiated into myofibroblasts. Two types of macrophages that exhibited phenotypic plasticity akin to M1 and M2 states were observed. We also identified novel signaling pathways involved in fibroblast and immune cell interaction in the hypertrophied LF, such as GAS and GRN, as well as known signaling pathways, such as TGF-β, PDGF, CXCL, and ANGPTL.
Our study shows the changing cellular composition and pathogenic signaling pathways involved during the process of chronic inflammation highlighting the transdifferentiation process from fibroblasts to myofibroblasts in the hypertrophied LF.
The identification of pathways such as GAS, GRN, TGF-β, ANGPTL, and CXCL, which appear to potentially contribute to LF hypertrophy, could significantly enhance our understanding of the pathogenesis of LSCS.
黄韧带（LF）是维持脊柱稳定性的关键结构；然而，黄韧带肥大是腰椎管狭窄症（LSCS）的重要原因。黄韧带肥大与腰椎管狭窄症加重之间的联系机制仍未完全明确。
本研究旨在探究肥大黄韧带中的细胞比例和信号通路。
从3例接受腰椎减压手术的患者获取黄韧带组织。这些患者在手术前被诊断为腰椎管狭窄症，且黄韧带厚度超过3.5毫米。
对黄韧带组织解离后进行单细胞RNA测序，并对数据进行质量控制、降维和聚类处理。差异基因表达和基因本体分析揭示了驱动黄韧带肥大的关键分子通路。通过细胞间通讯分析来阐明黄韧带组织内不同细胞类型之间的相互作用。
成纤维细胞占总细胞的75%，其次是内皮细胞、T细胞、巨噬细胞和B细胞。在不同类型的成纤维细胞中，我们发现一部分成纤维细胞转分化为肌成纤维细胞。观察到两种表现出类似于M1和M2状态表型可塑性的巨噬细胞。我们还确定了肥大黄韧带中参与成纤维细胞和免疫细胞相互作用的新信号通路，如GAS和GRN，以及已知的信号通路，如TGF-β、PDGF、CXCL和ANGPTL。
我们的研究显示了慢性炎症过程中细胞组成的变化和致病信号通路，突出了肥大黄韧带中成纤维细胞向肌成纤维细胞的转分化过程。
识别出如GAS、GRN、TGF-β、ANGPTL和CXCL等似乎可能导致黄韧带肥大的通路，可显著增强我们对腰椎管狭窄症发病机制的理解。
