Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: The Johnston county osteoarthritis project

Abstract

Objective. To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA.Methods. Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade >2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models.Results. Serum COMP levels were significantly elevated (P ‫؍‬ 0.0001) in the age >65 group (mean ؎ SD 1,302.1 ؎ 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 ؎ 432.4 and 1,038.6 ؎ 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 ؎ 487.47 ng/ml versus 1,061.83 ؎ 370.58 ng/ml; P ‫؍‬ 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P ‫؍‬ 0.0047), knee OA laterality (P ‫؍‬ 0.0043), and number of knee and hip joints involved (P ‫؍‬ 0.0001). There was no significant difference in serum COMP levels by gender or obesity.Conclusion. We demonstrate that in a populationbased sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.Osteoarthritis (OA) is the most common joint disease known, affecting ϳ16 million individuals in the US alone. The disease is characterized by functional deterioration of the joint and loss of cartilage integrity. Current research has focused on quantification of cartilage degeneration products released into the synovial fluid and, subsequently, into the blood as a measure of disease severity and as a potential tool for diagnosing OA in its early stages. The ability to objectively determine OA status serologically would significantly enhance capabilities of identifying the disease with greater ease and at lower cost than current radiographic methods.Cartilage oligomeric matrix protein (COMP) is a 524-kd pentameric glycoprotein related to the thrombospondin family and found predominantly in cartilage, although recent studies have identified COMP in both tendon and synovium (1-3). Serum and synovial fluid levels of COMP have been analyzed for their potential as diagnostic or prognostic markers for detecting OA onset or progression. Results of synovial fluid COMP analyses have varied. Compared with reference groups of healthy individuals or athletes lacking knee pain,

Characterization of metalloprotease cleavage products of human articular cartilage

“…COMP, a member of the thrombospondin family of proteins, has been shown to be increased in the serum of patients with OA and those with RA (38,39). In this study, MMP-12 was particularly active with respect to generating COMP-derived peptide fragments.…”

Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?

“…A few of these studies have also investigated the radiographic severity of OA and serum or urinary biochemical markers (18)(19)(20)(21)(22)(23). In the present study, we analyzed the largest panel of biochemical markers ever investigated in a wellcharacterized cohort of patients with knee OA and we observed that 14 of them were significantly associated with at least 1 imaging feature.…”

Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis

“…To our knowledge, this has not been done in previous studies of MMP-3 as a biomarker of OA. However, in a study of subjects with OA in which both hips and both knees were evaluated, Clark et al (31) reported that the serum level of cartilage oligomeric matrix protein (COMP) increased significantly with the number of affected joints. Similarly, Sowers et al (32) found that serum concentrations of the acute-phase reactant CRP were significantly higher among women with bilateral knee OA than among those with unilateral disease.…”