膝骨关节炎患者关节滑液中骨桥蛋白和软骨寡聚基质蛋白水平与疾病严重程度相关性
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作者Author单位AddressE-Mail
李晓云 LI Xiao-yun 岳阳市一人民医院脊柱科, 湖南 岳阳 414000 Department of Spine, Yueyang First People's Hospital, Yueyang 414000, Hunan, China a0w8g1@163.com 
沈正祥 SHEN Zheng-xiang 岳阳市一人民医院脊柱科, 湖南 岳阳 414000 Department of Spine, Yueyang First People's Hospital, Yueyang 414000, Hunan, China  
杨丹 YANG Dan 岳阳市一人民医院脊柱科, 湖南 岳阳 414000 Department of Spine, Yueyang First People's Hospital, Yueyang 414000, Hunan, China  
期刊信息:《中国骨伤》2022年,第35卷,第7期,第655-660页
DOI:10.12200/j.issn.1003-0034.2022.07.012
基金项目:
中文摘要:

目的:探讨膝骨关节炎(knee osteoarthritis,KOA)患者关节滑液中骨桥蛋白(osteopontin,OPN)和软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)水平与疾病严重程度的相关性。

方法:选取2018年2月至2020年5月收治的59例KOA患者作为KOA组,其中男25例,女34例;年龄60~75(65.57±1.56)岁;体质量指数(body mass index,BMI)21.4~30.7(26.12±1.54) kg/m2。采用Kellgren-Lawrence(K-L)分级对X线结果进行评估,其中Ⅱ级(K-L2组)14例,Ⅲ级(K-L3组)27例,Ⅳ级(K-L4组)18例。另选取18例因韧带或半月板疾病进行关节镜检查且无软骨损伤患者作为对照组,男7例,女11例;年龄61~78(64.88±1.60)岁;BMI 22.8~29.9(25.89±1.49) kg/m2。治疗前采集研究对象关节滑液样本,采用酶联免疫吸附试验检测关节滑液OPN、COMP水平,比较KOA组与对照组关节滑液OPN、COMP水平。比较不同K-L分级KOA患者性别、年龄、BMI等临床资料,采用酶联免疫试验检测其关节滑液中白细胞介素-1β(interleukin -1β,IL-1β),OPN,COMP,基质金属蛋白酶3(matrix metalloproteinase -3,MMP-3)水平,比较不同K-L分级KOA患者临床资料和生化指标,采用Logistic回归分析影响KOA患者K-L分级的因素,采用ROC曲线下面积(area under the curve,AUC)预测KOA疾病严重程度。

结果:59例KOA患者获得随访,时间8~27(15.75±3.27)个月。KOA组关节滑液OPN、COMP水平高于对照组(P<0.001)。K-L2组、K-L3组、K-L4组IL-1β、OPN、COMP、MMP-3水平比较差异有统计学意义(P<0.001);与K-L2组比较,K-L3、K-L4关节滑液关节滑液IL-1β、OPN、COMP、MMP-3 水平均升高(P<0.05);与K-L3组比较,K-L4关节滑IL-1β、OPN、COMP、MMP-3水平均升高(P<0.05)。多因素Logistic回归分析结果显示:关节滑液OPN、COMP、MMP-3水平是影响KOA患者K-L分级的独立危险因素(OR=6.653, 4.229,1.579,P<0.001)。关节滑液OPN预测K-L4级KOA的AUC为0.720[95%CI(0.588-0.851)],灵敏度为94.4%,特异度为65.9%;关节滑液COMP预测K-L4级KOA的AUC为0.731[95%CI(0.592-0.870)],灵敏度为88.9%,特异度为63.4%;关节滑液OPN联合COMP预测K-L4级KOA的AUC为0.839[95%CI(0.724-0.953)],灵敏度为94.4%,特异度为51.2%;OPN联合COMP预测K-L4级KOA的AUC大于单独OPN、COMP的AUC(Z=4.037,3.540,P<0.05)。

结论:KOA患者关节滑液OPN、COMP水平升高,并随着K-L分级增加而升高。关节滑液OPN、COMP是影响KOA患者K-L分级的独立危险因素,二者预测K-L4级KOA 的AUC、灵敏度、特异度高,可用于评估KOA疾病进展。
【关键词】骨关节炎,膝  关节滑液  骨桥蛋白  软骨寡聚基质蛋白
 
Correlation between osteopontin and cartilage oligomeric matrix protein levels in joint synovial fluid of patients with knee osteoarthritis and disease severity
ABSTRACT  

Objective: To investigate the correlation between osteopontin(OPN) and cartilage oligomeric matrix protein (COMP) levels in synovial fluid of patients with knee osteoarthritis(KOA) and the severity of the disease.

Methods: A total of 59 patients with KOA admitted to our hospital from February 2018 to May 2020 were selected as the KOA group, including 25 males and 34 females, age ranged 60 to 75 years old with an average of(65.57±1.56) years old, the body mass index(BMI) ranged 21.4 to 30.7(26.12±1.54) kg/m2. After admission, X-ray examination was performed, and Kellgren-Lawrence(K-L) grading system was used to evaluate the X-ray examination results. There were 14 cases in gradeⅡ(K-L2 group), 27 cases in grade Ⅲ(K-L3 group), and 18 cases in grade Ⅳ(K-L4 group). Eighteen patients who underwent arthroscopy for ligament or meniscus disease without cartilage damage were selected as control group, including 7 males and 11 females, age ranged 61 to 78 years old with an average of (64.88±1.60) years old, BMI ranged 22.8 to 29.9(25.89±1.49) kg/m2. Before treatment, synovial fluid samples of subjects were collected, and the OPN and COMP levels of synovial fluid were detected by Elisa. The OPN and COMP levels of synovial fluid in KOA group and control group were compared. The clinical data of KOA patients with different K-L grades were collected, including gender, age and BMI. The biochemical indices of interleukin-1 β(IL-1β), OPN, COMP and matrix metalloproteinase 3(MMP-3) in synovitic fluid were detected by enzyme-linked immunoassay, and the clinical data and biochemical indices of KOA patients with different K-L grades were compared. Logistic regression was used to analyze the factors affecting the K-L classification of KOA patients, and the area under the ROC curve(AUC) was used to predict the severity of KOA.

Results: All the 59 patients were followed up for 8 to 27(15.75±3.27) months. The levels of OPN and COMP in synovial fluid in KOA group were significantly higher than those in control group (t=16.991, 17.387, P<0.001). The levels of IL-1β, OPN, COMP and MMP-3 in synovitic fluid were significantly different among those in different K-L grade KOA patients(P<0.001). Compared with the K-L2 group, the levels of IL-1β, OPN, COMP, and MMP-3 in the synovial fluid of K-L3 and K-L4 were increased (P<0.05). Compared with the K-L3 group, the levels of IL-1β, OPN, COMP, and MMP-3 in the K-L4 joint were increased (P<0.05). Multivariate Logistic regression analysis showed that the levels of OPN, COMP and MMP-3 were independent risk factors for K-L grading of KOA patients(OR=6.653, 4.229, 1.579, P<0.001). AUC of OPN in synovial fluid predicting K-L4 KOA was 0.720[95%CI(0.588-0.851)], and the sensitivity was 94.4%. the specificity was 65.9%. The AUC of COMP in synoviac fluid predicting K-L4 KOA was 0.731[95%CI(0.592-0.870)], the sensitivity was 88.9%, the specificity was 63.4%. The AUC of OPN combined with COMP in synoviac fluid predicting K-L4 KOA was 0.839[95%CI(0.724-0.953)], the sensitivity was 94.4%, and the specificity was 51.2%. The AUC of OPN combined with COMP in synoviac fluid predicting K-L4 grade KOA was greater than that of OPN and COMP alone(Z=4.037, 3.540, P<0.05).

Conclusion: The levels of OPN and COMP in synovial fluid increase in patients with KOA, and they increase with the increase of K-L grade. Synovitic fluid OPN and COMP are independent risk factors affecting K-L grade of KOA patients, and they have high AUC, sensitivity and specificity in predicting of K-L4 KOA, and can be used to evaluate the progression of KOA disease.
KEY WORDS  Osteoarthritis, knee  Synovitic fluid  Osteopontin  Cartilage oligomeric matrix protein
 
引用本文,请按以下格式著录参考文献:
中文格式:李晓云,沈正祥,杨丹.膝骨关节炎患者关节滑液中骨桥蛋白和软骨寡聚基质蛋白水平与疾病严重程度相关性[J].中国骨伤,2022,35(7):655~660
英文格式:LI Xiao-yun,SHEN Zheng-xiang,YANG Dan.Correlation between osteopontin and cartilage oligomeric matrix protein levels in joint synovial fluid of patients with knee osteoarthritis and disease severity[J].zhongguo gu shang / China J Orthop Trauma ,2022,35(7):655~660
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