血清miR-30a-5p通过靶向FOXD1对膝骨关节炎发展的影响

张丹龙; 梁少博; 魏巍; 庄岩; 张堃

doi:10.16190/j.cnki.45-1211/r.2023.02.015

血清miR-30a-5p通过靶向FOXD1对膝骨关节炎发展的影响

Effect of serum miR-30a-5p on the development of knee osteoarthritis by targeting FOXD1

摘要

摘要: 目的：探讨膝骨关节炎（KOA）患者血清miR-30a-5p水平变化及其临床意义。方法：收集2019年1月至2022年1月西安交通大学医学院附属红会医院创伤骨科收治的253例KOA活动期患者（KOA组）和209例非KOA志愿者（对照组）的临床资料进行前瞻性分析。其中20例KOA患者接受全膝关节置换，25例对照组采用选择性膝关节镜探查清理术获取滑膜组织。采用实时荧光定量聚合酶链式反应（RT-qPCR）检测血清和滑液miR-30a-5p水平；采用western blotting法检测滑膜组织叉头框D1（FOXD1）蛋白表达。通过Spearman相关分析评估miR-30a-5p 与Kellgren-Lawrence（K-L）分级、西安大略大学和麦克马斯特大学骨关节炎指数（WOMAC）、膝关节疼痛数字等级评定量表（NRS）评分以及炎症指标的相关性。结果：KOA 组血清miR-30a-5p水平显著高于对照组2.32（1.92～3.20）vs.1.08（0.82～1.48），Z=-12.663，P< 0.001；受试者工作特征曲线（ROC）分析的灵敏度和特异性分别为83.80%和78.0%；KOA患者血清miR-30a-5p水平与WOMAC评分、膝关节疼痛NRS评分以及白细胞计数（WBC）、红细胞沉降率（ESR）、C-反应蛋白（CRP）均呈正相关关系（P< 0.05）。78 例首次诊断KOA 患者治疗4 周后血清miR-30a-5p水平较基线值显著降低（P< 0.001）。另外20例KOA患者滑膜组织中FOXD1蛋白表达较对照组下调（P< 0.001），且血清miR-30a-5p 水平与滑膜组织中FOXD1 蛋白表达呈负相关关系（P< 0.001），与滑液中miR-30a-5p 水平呈正相关关系（P< 0.001）。结论：血清miR-30a-5p水平的升高可能通过抑制FOXD1促进KOA的进展，血清miR-30a-5p可能成为KOA诊断和评估的潜在指标。

Abstract: Objective: To explore the changes and clinical significance of serum miR-30a-5p in patients with knee osteoarthritis (KOA).Methods: A prospective analysis was performed on clinical data of 253 patients with active KOA (KOA group) and 209 non-KOA volunteers (control group) admitted to Department of Orthopedic Trauma, HongHui Hospital Affiliated to Xi’an Jiaotong University Health Science Center from January 2019 to January 2022.Among them, 20 KOA patients received total knee arthroplasty, and 25 patients in the control group received synovial tissue with selective knee arthroscopic exploration and cleaning.The level of miR-30a-5p in serum and synovial fluid was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR); western blotting was used to detect the expression of forkhead box D1 (FOXD1) protein in synovial tis-sue.Spearman correlation analysis was used to evaluate the correlation between miR-30a-5p and Kellgren-Law-rence (K-L) scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee pain Nu-merical Rating Scale(NRS)scores and inflammatory markers.Results: The serum miR-30a-5p level was signifi-cantly higher in the KOA group than that in the control group 2.32(1.92-3.20)vs 1.08(0.82-1.48), Z=-12.663, P< 0.001.The serum miR-30a-5p level in KOA patients was positively correlated with WOMAC score, knee pain NRS score, white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP)(P< 0.05).Serum miR-30a-5p level significant-ly decreased from baseline after 4 weeks of treatment in 78 patients first diagnosed with KOA(P< 0.001).The expression of FOXD1 protein in synovial tissue of other 20 patients with KOA was down-regulated compared with the control group(P< 0.001), and positively correlated with the level of miR-30a-5p in synovial fluid (P< 0.001).Conclusion: Elevated serum miR-30a-5p level may promote the progression of KOA by inhibiting FOXD1.Therefore, serum miR-30a-5p may be an indicator for the diagnosis and evaluation of KOA.

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