Correlation between osteopontin and cartilage oligomeric matrix protein levels in joint synovial fluid of patients with knee osteoarthritis and disease severity

Abstract

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. 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. 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). 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.