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

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".

Combined detection of COMP and CS846 biomarkers in experimental rat osteoarthritis: a potential approach for assessment and diagnosis of osteoarthritis

“…Also, the increase in SF COMP levels correlated with the length of time post injury, suggesting that COMP may be a suitable marker for longitudinal studies to evaluate its role in joint healing [ 28 ]. Georgiev et al observed higher serum COMP levels in knee OA patients when compared to controls, and COMP correlated positively with Whole-Organ MRI Score, suggesting that COMP may reflect structural damage of the knee joint [ 29 ].…”

Multifaceted Protective Role of Glucosamine against Osteoarthritis: Review of Its Molecular Mechanisms

“…Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), are produced by activated synoviocytes, chondrocytes and mononuclear cells, upregulate the expression of matrix metalloproteinases (MMPs) and degrade the cartilage matrix [8]. Various biomarkers, including inflammatory markers (IL-1β and TNF-α), MMPs, and matrix degradation markers (cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen (CTX-II), and N-terminal type I collagen telopeptide), can be used to detect OA progression [9][10][11]. COMP is a 535-kDa non-collagenous protein related to the thrombospondin family and is primarily found in the articular cartilage, tendons, and synovium [11,12].…”

Association of Circulating COMP and YKL-40 as Markers of Metabolic Changes of Cartilage with Adipocytokines in Juvenile Idiopathic Arthritis

“…Additionally, we suggest that YKL-40 may be a useful biomarker of disease activity and may be used to assess treatment towards remission, as compared to COMP.Metabolites 2020, 10, 61 2 of 11 remodeling, manifested by significant changes of the circulating markers of cartilage turnover, including total glycosaminoglycans (GAGs) and their particular types such as keratan sulphate, chondroitin sulphate, hyaluronic acid, as well as chondroitin sulphate 846 epitope [5][6][7][8].Among ECM components, which are indicators of the cartilage breakdown, there are also listed components synthesized by chondrocytes, i.e., cartilage oligomeric matrix protein (COMP) as well as human cartilage glycoprotein 39 (YKL-40), that are so far not evaluated in JIA patients. The first one is a non-collagenous glycoprotein, binding to aggrecan; fibronectin; and collagen types I, II, and IX, which seem to play a role in the structure of fibrils and in maintenance of the collagen network [9,10]. Whereas YKL-40, a glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate autoantigen in rheumatoid arthritis.…”

“…It has been shown that YKL-40 binds to some important components in the cartilage extracellular matrix, i.e., proteoglycans and collagens, influencing their production and assembly [11][12][13][14]. Several authors have investigated the relationship between circulating COMP or YKL-40 and the condition of articular cartilage in adult patients with and without any rheumatic disease [9][10][11][12][13][14][15][16][17][18][19]. A correlation between the degree of articular cartilage degradation expressed by COMP level but not by YKL-40 and the adipose tissue content has been observed in the patients [15].…”

“…Among ECM components, which are indicators of the cartilage breakdown, there are also listed components synthesized by chondrocytes, i.e., cartilage oligomeric matrix protein (COMP) as well as human cartilage glycoprotein 39 (YKL-40), that are so far not evaluated in JIA patients. The first one is a non-collagenous glycoprotein, binding to aggrecan; fibronectin; and collagen types I, II, and IX, which seem to play a role in the structure of fibrils and in maintenance of the collagen network [9,10]. Whereas YKL-40, a glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate autoantigen in rheumatoid arthritis.…”