Liu Yuhang, Huang Lina, Gao Zhengtian, Hou Yingnuo, Kong Fanlei, Hou Shibin, Li Zheng
Orthopedics Department II, The First Affiliated Hospital of Harbin Medical University, Harbin, 150006, China.
Department of Rehabilitation Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.
J Orthop Surg Res. 2025 Jul 21;20(1):690. doi: 10.1186/s13018-025-06069-4.
Previous studies show that about 80% of lumbar disc degeneration (LDD) patients experience back or leg pain, affecting their quality of life. However, the causes of LDD are not fully understood. This study focused on exploring the expression level of miR-340-5p and SRY-related high-mobility-group box 4 (SOX4) in LDD and attempts to clarify its potential mechanism in the pathological process of LDD.
A total of 88 patients with LDD and 80 non-LDD patients were continuously included in this study. The miR-340-5p levels in nucleus pulposus (NP) tissues were measured using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). The potential diagnostic significance of miR-340-5p for LDD was evaluated by generating a Receiver Operating Characteristic (ROC) curve. The impacts of miR-340-5p on Lipopolysaccharide (LPS)-stimulated NP cells were analyzed through the Cell Counting Kit-8 (CCK-8) method, and apoptosis levels were quantified using flow cytometry. Additionally, the concentrations of inflammatory cytokines and extracellular matrix (ECM) remodeling markers were assessed with Enzyme-Linked Immunosorbent Assay (ELISA) kits.
miR-340-5p was abnormally down-regulated in LDD patients and the ROC curve showed that miR-340-5p has diagnostic value for LDD (AUC = 0.909, sensitivity = 81.8%, specificity = 85.0%, cutoff value = 0.815). Additionally, the enforced expression of miR-340-5p promoted proliferation and ECM remodeling and inhibited the level of apoptosis and pro-inflammatory factors in LPS-damaged NP cells. However, overexpression of SOX4 counteracted the effects of miR-340-5p overexpression on LPS-induced NP cells.
miR-340-5p alleviates the damage effect of LPS on NP cells by negatively regulating the SOX4, and miR-340-5p may be a potential therapeutic target for LDD.
先前的研究表明，约80%的腰椎间盘退变（LDD）患者会经历背痛或腿痛，影响其生活质量。然而，LDD的病因尚未完全明确。本研究聚焦于探究miR-340-5p和SRY相关高迁移率族蛋白盒4（SOX4）在LDD中的表达水平，并试图阐明其在LDD病理过程中的潜在机制。
本研究连续纳入了88例LDD患者和80例非LDD患者。采用逆转录定量聚合酶链反应（RT-qPCR）检测髓核（NP）组织中miR-340-5p的水平。通过绘制受试者工作特征（ROC）曲线评估miR-340-5p对LDD的潜在诊断意义。采用细胞计数试剂盒-8（CCK-8）法分析miR-340-5p对脂多糖（LPS）刺激的NP细胞的影响，并使用流式细胞术定量凋亡水平。此外，使用酶联免疫吸附测定（ELISA）试剂盒评估炎性细胞因子和细胞外基质（ECM）重塑标志物的浓度。
miR-340-5p在LDD患者中异常下调，ROC曲线显示miR-340-5p对LDD具有诊断价值（AUC = 0.909，敏感性 = 81.8%，特异性 = 85.0%，截断值 = 0.815）。此外，miR-340-5p的过表达促进了LPS损伤的NP细胞的增殖和ECM重塑，并抑制了凋亡水平和促炎因子。然而，SOX4的过表达抵消了miR-340-5p过表达对LPS诱导的NP细胞的影响。
miR-340-5p通过负向调节SOX4减轻LPS对NP细胞的损伤作用，miR-340-5p可能是LDD的潜在治疗靶点。
