目的:观察膝骨关节炎(knee osteoarthritis, KOA)患者血清miR-142-3P在不同临床分期中表达的差异,分析其严重程度与炎症因子表达的相关性。方法:选取2021年12月至2022年9月在包头医学院第一附属医院骨科门诊和住院处诊断为膝骨关节炎的患者60例为观察组,根据中华医学会《骨关节炎诊疗指南》(2018年版)和Kellgren-Lawrence分级,分为早、中、晚期,每组20例,20例健康体检者为对照组;反转录-聚合酶链反应、酶联免疫吸附测定法分别检测血清中miR-142-3P和炎症因子IL-6、IL-1β、TNF-α的表达水平;应用Spearman相关检验分析KOA患者血清miR-142-3P与临床分期以及炎症因子表达的相关性。结果:(1)与对照组相比,miR-142-3P表达在观察组中早、中、晚期均升高,差异有统计学意义(P＜0.05),晚期表达量比中期下降;与对照组相比,IL-6表达在观察组中早、中、晚期均升高,差异有统计学意义(P＜0.05),晚期较中期表达量降低;与对照组相比,IL-1β表达在观察组中早、中、晚期均升高,差异有统计学意义(P＜0.05);与对照组相比,TNF-α表达在观察组中早、中、晚期均升高,差异有统计学意义(P＜0.05);(2)miR-142-3P表达量与KOA临床分期呈正相关(r=0.450,P=0.000);IL-6与KOA临床分期呈正相关(r=0.405 5,P=0.001 3),IL-1β与KOA临床分期呈正相关(r=0.938,P＜0.000 1),TNF-α与KOA临床分期呈正相关(r=0.943,P＜0.000 1);(3)miR-142-3P表达量与IL-6呈正相关(r=0.699 0,P＜0.000 1),与IL-1β呈正相关(r=0.5048,P＜0.000 1),与TNF-α呈正相关(r=0.514 7,P＜0.000 1)。结论:miR-142-3p与KOA分期呈正相关,miR-142-3P表达与炎症因子IL-6、IL-1β、TNF-α存在正相关。
Objective: To study the correlation of disease severity with the expression of inflammatory factors by analyzing the differences in expression of serum miR-142-3P in different clinical stages of patients with knee osteoarthritis (KOA). Methods: A total of 60 patients who diagnosed as KOA in the First Affiliated hospital of Baotou Medical College were selected as the observation group, they were divided into three groups according to the Kellgren-Lawrence classification and Chinese Medical Association Guidelines for the Diagnosis and Treatment of Osteoarthritis (2018 edition), which are the groups of early, middle and late stages, with 20 patients in each group. A total of 20 healthy subjects were selected as the control group. The expression levels of miR-142-3P and inflammatory factors IL-6, IL-1β and TNF-α were measured using reverse transcript-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). SPSS 23.0 Statistical software was used to analyze expression variability, and Spearman correlation analysis was used to analyze relationship between serum miR-142-3P and clinical stage as well as expression of inflammatory factors in KOA patients. Results: Compared with the control group, miRNA-142-3P expressions were increased in the early, middle and late stages of the observation group, and the differences were statistically significant (P＜0.05), and it was lower in the late stage than that in the middle stage. Compared with the control group, IL-6 expressions were increased in the early, middle and late stages of the observation group, and the differences were statistically significant (P＜0.05), and it was lower in the late stage than that in the middle stage. Compared with the control group, IL-1 β expression was increased in the early, middle and late stages of the observation group, and the differences were statistically significant (P＜0.05). Compared with the control group, TNF- α expression was increased in the early, middle and late stages, and the differences were statistically significant (P＜0.05). The miRNA-142-3P, IL-6, IL-1β and TNF-α expression levels were all positively correlated with the clinical stage of KOA (respectively, r=0.450, P=0.000;r=0.405 5, P=0.001 3;r=0.938, P＜0.000 1;r=0.943, P＜0.000 1). The expression level of miRNA-142-3P was positively correlated with IL-6 (r=0.699 0, P＜0.000 1), IL-1β(r=0.504 8, P＜0.000 1) and TNF-α (r=0.514 7, P＜0.000 1). Conclusion: miRNA-142-3p expression is positively correlated with KOA stages, as well as inflammatory cytokines IL-6, IL-1 β, and TNF- α.
[1] Sharma L. Osteoarthritis of the Knee[J]. N Engl J Med, 2021, 384(1): 51-59.
[2] Mandl LA. Osteoarthritis year in review 2018: clinical[J]. Osteoarthritis Cartilage, 2019, 27(3): 359-364.
[3] 王琦, 易诚青. 膝关节骨关节炎治疗的研究进展[J]. 复旦学报(医学版), 2022, 49(5): 765-770.
[4] Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, et al. An overview of microRNAs: biology,functions,therapeutics,and analysis methods[J]. J of Cell Physiol, 2019, 234(5): 5451-5465.
[5] 魏萌, 张英民, 康少英, 等. miR-142-3p靶向PERK/Bip信号通路对骨关节炎模型大鼠的干预作用[J]. 局解手术学杂志, 2022, 31(5): 379-383.
[6] 赵涌. miR-142-3p在类风湿关节炎中的表达及作用机制[D]. 郑州: 郑州大学, 2016.
[7] Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: kellgren-lawrence classification of osteoarthritis[J]. Clin Orthop Relat Res, 2016, 474(8): 1886-1893.
[8] 骨关节炎诊疗指南(2018年版)[J]. 中华骨科杂志, 2018, 38(12): 705-715.
[9] 王海英, 丁晓, 杨立, 等. 不同分期骨关节炎关节液中相关降解酶的表达差异[J]. 中国组织工程研究, 2019, 23(23): 3609-3615.
[10] 郭保逢, 秦泗河, 黄野. 膝关节骨关节炎的保膝治疗进展[J]. 中国修复重建外科杂志, 2018, 32(10): 1292-1296.
[11] 董天华. 膝关节骨性关节炎的基础与临床研究[D]. 河北医科大学, 2016.
[12] He BX, Zhao ZY, Cai QD, et al. miRNA-based biomarkers,therapies, and resistance in cancer[J]. Int J Biol Sci, 2020, 16(14): 2628-2647.
[13] Li H, Yang HH, Sun ZG, et al. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients[J]. Bone & Joint Research, 2019, 8(7): 290-303.
[14] 张振辉, 江子欣, 杨其霖, 等. miR-142-3p对THP-1细胞释放炎症因子的调控作用[J]. 广东医学, 2014, 35(2): 180-183.
[15] Wiegertjes R, van Caam A, van Beuningen H, et al. TGF-β dampens IL-6 signaling in articular chondrocytes by decreasing IL-6 receptor expression[J]. Osteoarthritis Cartilage, 2019, 27(8): 1197-1207.
[16] Cajas Santana LJ, Rondón Herrera F, Rojas AP, et al. Serum chemerin in a cohort of colombian patients with primary osteoarthritis[J]. Reumatol Clin, 2021, 17(9): 530-535.
[17] Sakurai Y, Fujita M, Kawasaki S, et al. Contribution of synovial macrophages to rat advanced osteoarthritis pain resistant to cyclooxygenase inhibitors[J]. Pain, 2019, 160(4): 895-907.
[18] Zhang HY, Lin CX, Zeng C, et al. Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2[J]. Ann Rheum Dis, 2018, 77(10): 1524-1534.
[19] Wiegertjes R, van De Loo FA J, Blaney Davidson EN. A roadmap to target interleukin-6 in osteoarthritis[J]. Rheumatology(Oxford, England), 2020, 59(10): 2681-2694.
[20] Rai PK, Singh AK, Singh OP, et al. Efficacy of leech therapy in the management of osteoarthritis(Sandhivata)[J]. Ayu, 2011, 32(2): 213-217.
[21] Larsson S, Englund M, Struglics A, et al. Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy[J]. Osteoarthritis Cartilage, 2015, 23(11): 1906-1914.
