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软骨寡聚蛋白、基质金属蛋白酶-3 和 Coll2-1 作为膝关节骨关节炎的血清生物标志物:一项横断面研究。

Cartilage oligomeric protein, matrix metalloproteinase-3, and Coll2-1 as serum biomarkers in knee osteoarthritis: a cross-sectional study.

机构信息

Clinic of Rheumatology, University Hospital "St. Ivan Rilski", Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.

Laboratory of Clinical Immunology, University Hospital "Lozenets", Medical Faculty, Sofia University, Sofia, Bulgaria.

出版信息

Rheumatol Int. 2018 May;38(5):821-830. doi: 10.1007/s00296-017-3887-y. Epub 2017 Nov 21.

DOI:10.1007/s00296-017-3887-y
PMID:29164307
Abstract

Biochemical markers reflecting joint remodeling in osteoarthritis (OA) are a promising diagnostic tool. The aim of this study was to investigate serum levels of candidate biomarkers in subjects with and without knee OA and assess their correlation with clinical parameters and knee structural damage. 56 patients with primary knee OA and 31 healthy controls participated in this study. Patients were separated into two groups: isolated knee OA and generalized OA. Clinical parameters were obtained by validated self-reported questionnaires and a visual analogue scale. Serum levels of cartilage oligomeric protein (COMP), matrix metalloproteinase-3 (MMP-3), and Coll2-1 were quantified by enzyme-linked immunosorbent assay. Knee structural damage was determined by plain X-ray and 1.5 T magnetic resonance imaging (MRI), using Kellgren-Lawrence (KL) grading scale and Whole-Organ Magnetic Resonance Imaging Score (WORMS), respectively. Compared to controls, patients had significantly higher median serum COMP (985 vs. 625 ng/ml; p < 0.001) and MMP-3 (36.85 vs. 22.10 ng/ml; p = 0.003) levels. Patients with radiographic evidence of KLII/III knee OA had greater median COMP levels than KLI patients (1095 vs. 720 ng/ml; p = 0.001). In the generalized OA group, mean MMP-3 levels were higher than in the isolated knee OA group (30.40 vs. 55.13 ng/ml; p < 0.001). COMP correlated positively with WORMS (r  = 0.454, p < 0.001) and MMP-3 (r  = 0.337, p = 0.003). Cut-off values for serum COMP and MMP-3 were determined. We observed higher serum COMP and MMP-3 levels in knee OA patients compared to controls. COMP may reflect knee structural damage, while MMP-3-OA "generalization".

摘要

反映骨关节炎(OA)关节重塑的生化标志物是一种很有前途的诊断工具。本研究旨在探讨伴有和不伴有膝 OA 的患者候选生物标志物的血清水平,并评估其与临床参数和膝关节结构损伤的相关性。56 例原发性膝 OA 患者和 31 例健康对照者参与了本研究。患者分为两组:单纯膝 OA 和全身 OA。临床参数采用经过验证的自我报告问卷和视觉模拟量表获得。采用酶联免疫吸附试验定量测定软骨寡聚蛋白(COMP)、基质金属蛋白酶-3(MMP-3)和 Coll2-1 的血清水平。通过普通 X 射线和 1.5 T 磁共振成像(MRI)确定膝关节结构损伤,分别采用 Kellgren-Lawrence(KL)分级量表和全器官磁共振成像评分(WORMS)。与对照组相比,患者的血清 COMP(985 与 625ng/ml;p<0.001)和 MMP-3(36.85 与 22.10ng/ml;p=0.003)水平明显更高。影像学表现为 KLII/III 膝关节 OA 的患者 COMP 水平中位数高于 KL I 患者(1095 与 720ng/ml;p=0.001)。在全身 OA 组中,MMP-3 水平均高于单纯膝 OA 组(30.40 与 55.13ng/ml;p<0.001)。COMP 与 WORMS 呈正相关(r=0.454,p<0.001)和 MMP-3(r=0.337,p=0.003)。确定了血清 COMP 和 MMP-3 的截断值。与对照组相比,我们观察到膝关节炎患者的血清 COMP 和 MMP-3 水平较高。COMP 可能反映膝关节结构损伤,而 MMP-3 反映 OA“泛化”。

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