Is pro-matrix metalloproteinase-3 a marker for posttraumatic cartilage degradation? (original) (raw)
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Rheumatology International, 2017
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 s = 0.454, p < 0.001) and MMP-3 (r s = 0.337, p = 0.003). Cutoff 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".
Serum cartilage oligomeric matrix protein: is there a repeated bout effect?
Orthopedic Reviews, 2014
The primary aim of the present study was to investigate if there is a repeated bout effect for cartilage tissue, evident in the marker serum cartilage oligomeric matrix protein (sCOMP). Ten healthy male subjects (26.4±3.14 years) performed two high impact interventions (100 drop jumps with a 30 second interval) carried out at a 3 week interval. After each intervention, sCOMP and muscle soreness were assessed on 8 and 6 occasions respectively. Muscle soreness was determined via a visual analog scale with a maximum pain score of 10. sComp levels did not show a blunted response after the second bout (Bout 1: 12.2±3.3 U/L−1; Bout 2: 13.1±4.0 U/L−1; P>0.05). Remarkably, sCOMP increased from baseline levels by 16% after bout 1 and 15% after bout 2. Muscle soreness was blunted following the second intervention (Bout 1: 5.0±1.8; Bout 2: 1.6±0.8). Unlike the known repeated bout effect for muscle damage markers, sCOMP levels do not show a blunted response after two similar loading interven...
Collagen type II C-telopeptide fragments as an index of cartilage degradation
Bone, 2001
We report the development of an assay for measurement of the urinary concentration of collagen type II C-telopeptide fragments. This assay was developed for providing a specific marker of joint metabolism. A monoclonal antibody, recognizing a linear six amino acid epitope from the middle region of the collagen type II C-telopeptide was used in a competitive enzyme-linked immunoassay (ELISA) format for measurement of urine samples. The technical performance and specificity of the assay was evaluated and a panel of samples from patients with rheumatoid arthritis (RA) (n ؍ 27), osteoarthritis (OA) (n ؍ 29), Paget's disease (n ؍ 9), and healthy controls (n ؍ 428) was measured in the assay. The ELISA was specific for the peptide EKGPDP derived from collagen type II C-telopeptide: it did not recognize peptides from the N-telopeptide of the molecule or from other collagen types. Collagen type II C-telopeptide fragments measured in the assay resisted seven freeze-thaw cycles and >20 h of storage at room temperature. RA and OA patients showed significant 2.33-fold (95% confidence interval [CI] 1.50-3.16) and 1.53-fold (CI 1.24-1.82) elevations in CartiLaps concentration, respectively. Paget's disease patients did not have elevated CartiLaps levels. RA patients with radiological evidence of cartilage damage had significantly higher (1.79-fold, CI 1.04-2.54) CartiLaps levels than RA patients without radiological evidence of cartilage destruction. The Cartilaps assay showed high technical precision and an ability to differentiate populations with an elevated joint metabolism from normal controls. This suggests that the assay may have clinical value in assisting in the diagnosis of joint diseases and in monitoring progression and therapy in RA and OA. (Bone 29:209-215; 2001
Cartilage, 2011
Objective: To determine the intraday and interday reliability of serum cartilage oligomeric matrix protein (sCOMP) in a physically active population with no history of lower extremity surgery. Design: A repeated-measures reliability study was employed to determine the intraday and interday reliability of sCOMP in a physically active cohort. A total of 23 subjects were recruited to the laboratory on 3 separate occasions for nonfasting serum collection. Subjects had no history of lower extremity surgery and were free from acute injury within the last 3 months. Results: Our results indicate strong reliability for both intraday intraclass correlation coefficient (ICC) (0.76) and interday ICC (0.74) sCOMP values. Conclusion: Our results demonstrate that following 30 minutes of inactivity, nonfasting serum samples remain stable over the course of 1 day and between 2 consecutive days in a healthy population with no history of lower extremity surgery. Future research studies are needed to further investigate the magnitude of change in this biomarker for patients with acute articular cartilage damage to determine its appropriateness for use in this population and for varying degrees of articular cartilage severity.
Osteoarthritis and Cartilage, 2012
Objective: To evaluate the hypothesis that a mechanical stimulus (30-min walk) will produce a change in serum concentrations of cartilage oligomeric matrix protein (COMP) that is associated with cartilage thickness changes on magnetic resonance imaging (MRI). Methods: Serum COMP concentrations were measured by enzyme-linked immunosorbent assay in 17 patients (11 females, age: 59.0 AE 9.2 years) with medial compartment knee osteoarthritis (OA) at study entry immediately before, immediately after, 3.5 h, and 5.5 h after a 30-min walking activity. Cartilage thickness changes in the medial femur and medial tibia were determined from MR images taken at study entry and at 5-year follow-up. Relationships between changes in cartilage thickness and COMP levels, with post-activity concentrations expressed as a percentage of pre-activity levels, were assessed by the calculation of Pearson correlation coefficients and by multiple linear regression analysis, with adjustments for age, sex, and body mass index (BMI). Results: Changes in COMP levels 3.5 h and 5.5 h post-activity were correlated with changes in cartilage thickness in the medial femur and tibia at the 5-year follow-up. The results were strengthened after analyses were adjusted for age, sex, and BMI. Neither baseline pre-activity COMP levels nor changes in COMP levels immediately post-activity were correlated with cartilage thickness changes. Conclusions: The results of this study support the hypothesis that a change in COMP concentration induced by a mechanical stimulus is associated with cartilage thinning at 5 years. Mechanically-induced changes in mechano-sensitive biomarkers should be further explored in the context of stimuluseresponse models to improve the ability to assess OA progression. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
Arthritis & Rheumatism, 1999
Aim of the work: The objective of our study was to determine the utility of serum cartilage oligomeric matrix protein (COMP) as a serum biomarker for hemophilic arthropathy and to evaluate the degree of joint damage radiologically using plain X-ray and functionally using functional independence score of hemophilia (FISH) and to study their relation with COMP. Patients and methods: The study was carried out on 30 boys with hemophilic arthropathy (group I) and 20 healthy boys as control (group II). All hemophiliacs patients were scored for FISH and radiological changes (Pettersson's score). Factor activity level was measured in group I while COMP was measured in both groups. Results: The patients' age ranged from 6 to 16 years (mean 10.6 ± 2.7 years). The knee was the most commonly affected joint (83.3%). Fifteen patients (50%) had severe hemophilia, 7 had moderate and 8 had mild hemophilia. Mean serum levels of COMP in hemophilic patients (529 ± 288.1 ng/ml) were significantly higher than in control (285 ± 63.2 ng/ml) (p = 0.014). The COMP level was significantly higher in patients with severe hemophilia compared to those with moderate or mild disease (p < 0.001). The serum COMP significantly correlated with joint space narrowing (r = 0.64, p < 0.001) and with the total Pettersson score (r = 0.42, p = 0.02) and negatively with the FISH score (r = À0.44, p = 0.016). Conclusions: Serum COMP level is indicative of the amount of joint damage in patients with hemophilic arthropathy. The combined scoring of functional independence and Pettersson score in addition to serum levels of COMP give a good overview of the degree of hemophilic arthropathy.
Modern Rheumatology, 2004
This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES);