Department of Orthopaedics and Trauma Surgery, Medical Centre, Faculty of Medicine, Albert Ludwig University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg,
Eur Cell Mater. 2020 Oct 2;40:115-132. doi: 10.22203/eCM.v040a07.
Symptomatic intervertebral disc (IVD) degeneration accounts for significant socioeconomic burden. Recently, the expression of the tissue renin-angiotensin system (tRAS) in rat and bovine IVD was demonstrated. The major effector of tRAS is angiotensin II (AngII), which participates in proinflammatory pathways. The present study investigated the expression of tRAS in human IVDs, and the correlation between tRAS, inflammation and IVD degeneration. Human IVD tissue was collected during spine surgery and distributed according to principal diagnosis. Gene expression of tRAS components, proinflammatory and catabolic markers in the IVD tissue was assessed. Hydroxyproline (OHP) and glycosaminoglycan (GAG) content in the IVD tissue were determined. Tissue distribution of tRAS components was investigated by immunohistochemistry. Gene expression of tRAS components such as angiotensin-converting enzyme (ACE), Ang II receptor type 2 (AGTR2), angiotensinogen (AGT) and cathepsin D (CTSD) was confirmed in human IVDs. IVD samples that expressed tRAS components (n = 21) revealed significantly higher expression levels of interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5 compared to tRAS-negative samples (n = 37). Within tRAS-positive samples, AGT, matrix-metalloproteinases 13 and 3, IL-1, IL-6 and IL-8 were more highly expressed in traumatic compared to degenerated IVDs. Total GAG/DNA content of non-tRAS expressing IVD tissue was significantly higher compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD. The present study identified the existence of tRAS in the human IVD and suggested a correlation between tRAS expression, inflammation and ultimately IVD degeneration.
症状性椎间盘（IVD）退变会造成巨大的社会经济负担。最近，研究人员在大鼠和牛的 IVD 中证实了组织肾素-血管紧张素系统（tRAS）的表达。tRAS 的主要效应物是血管紧张素 II（AngII），它参与了促炎途径。本研究调查了 tRAS 在人 IVD 中的表达，以及 tRAS、炎症和 IVD 退变之间的相关性。在脊柱手术过程中收集人 IVD 组织，并根据主要诊断进行分配。评估 IVD 组织中 tRAS 成分、促炎和分解代谢标志物的基因表达。测定 IVD 组织中的羟脯氨酸（OHP）和糖胺聚糖（GAG）含量。通过免疫组织化学研究 tRAS 成分的组织分布。在人 IVD 中证实了 tRAS 成分（如血管紧张素转换酶（ACE）、血管紧张素 II 受体 2（AGTR2）、血管紧张素原（AGT）和组织蛋白酶 D（CTSD））的基因表达。表达 tRAS 成分的 IVD 样本（n = 21）与 tRAS 阴性样本（n = 37）相比，白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）、解整合素金属蛋白酶与血小板反应蛋白 4 和 5（ADAMTS）4 和 5 的表达水平显著升高。在 tRAS 阳性样本中，与退变相比，创伤性 IVD 中 AGT、基质金属蛋白酶 13 和 3、白细胞介素 1、白细胞介素 6 和白细胞介素 8 的表达更高。非 tRAS 表达 IVD 组织的总 GAG/DNA 含量明显高于 tRAS 阳性组织。免疫组织化学证实了 AngII 存在于人 IVD 中。本研究鉴定了 tRAS 在人 IVD 中的存在，并提出了 tRAS 表达、炎症与最终 IVD 退变之间的相关性。
