Cartilage Oligomeric Matrix Protein Levels Research Articles

Effect of increased mechanical knee joint loading during running on the serum concentration of cartilage oligomeric matrix protein (COMP).

The purpose of the study was to investigate the effect of an increase in mechanical knee joint loading during running on the serum COMP level. On two different test days, 20 healthy men ran with knee orthoses for 30 min on a treadmill (v = 2.2 m/s). On day 1, the orthoses were passive, whereas on day 2 they were pneumatically driven (active) and thus increased the external knee flexion moments (+30.9 Nm) during stance phase. Lower-limb mechanics and serum COMP levels (baseline; 0, 0.5, 1, 2 h post running) were analyzed. COMP levels increased immediately after running with passive (+35%; pre: 7.5 U/l, 95%CI: 6.4, 8.7, post: 9.8 U/l, 95%CI: 8.8, 10.8, p < 0.001) and active orthoses (+45%; pre: 7.6 U/l; 95%CI: 6.4, 8.8, post: 10.3 U/l, 95%CI: 9.2, 11.5, p < 0.001), but they did not differ between interventions. While running with active orthoses, greater ankle dorsiflexion angles, knee flexion angles, and moments occurred (p < 0.05). Comparing both interventions, the Δ COMP pre-post, meaning the difference (Δ) between running with active and passive orthoses in pre to post COMP level change (=level after (post) running minus level before (pre) running), correlated negatively with Δ COMP baseline (difference between the baseline COMP level before running with active and passive orthoses, r = -0.616; p = 0.004), and with a positive tendence with the Δ maximum knee flexion (r = 0.388; p = 0.091). Therefore, changes in COMP concentration after physical activity seem to be highly influenced by the COMP baseline level. In addition, correlation analysis indicates that modifications in knee joint kinematics have a greater effect on cartilage metabolism than an increase in joint moments. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1937-1946, 2018.

Role of cartilage oligomeric matrix protein (COMP) as a prognostic biomarker in follow-up of early rheumatoid arthritis patients: Correlation to musculoskeletal ultrasonographic findings

Aim of the workTo assess the level of serum cartilage oligomeric matrix protein (COMP) in early rheumatoid arthritis (RA) patients and study its relation to disease activity and musculoskeletal ultrasound (MSUS) findings. Patients and methodsThe study included 40 early RA patients. Disease activity score (DAS28) was assessed. Serum COMP level was measured and MSUS findings of the small joints of hands done at base line and after 6 months of follow up.20 age and sex matched control were included. ResultsPatients age was 38.8 ± 9.3 years; 36 females and 4 males and disease duration 6.7 ± 3.5 years. Serum COMP was significantly higher in patients (median 190 U/L; 90–750 U/L) compared to control (90 U/L; 80–130 U/L)(p < .001) being higher in more active (250 U/L) (p = .001) and significantly correlated with baseline synovial inflammation (p = .009). COMP levels were lowered after 6 months of receiving treatment (110 U/L; 30–180 U/L) (p < .001). The presence of bony erosions increased with more active disease (p = .003). There was a significant reduction in the erythrocyte sedimentation rate and COMP at follow up (p < .0001 and p = .001 respectively). No correlation was found between the COMP level with C-reactive protein, ESR, MSUS score or bony erosions at follow up. ConclusionsCOMP significantly correlated with disease activity in early RA and could be used as a marker of activity. It correlates significantly with synovial inflammation detected by power Doppler. COMP may reflect the outcome and could be used as a prognostic marker in RA patients. COMP did not significantly correlate with bone erosions.

Meta-analysis of serum C-reactive protein and cartilage oligomeric matrix protein levels as biomarkers for clinical knee osteoarthritis

BackgroundThe roles of C-reactive protein (CRP) and cartilage oligomeric matrix protein (COMP) in knee osteoarthritis (KOA) remain controversial, thus the present study is aimed to explore the relationships between CRP, COMP, and the incidence/progression of KOA.MethodsA systematic search was conducted on PubMed and Embase until September, 2016 for all the relevant studies. The pooled mean difference (MD) with its 95% confidence interval (95% CI) based on fixed effects model or random effects model was calculated to assess the potential role of CRP and COMP in the incidence or progression of KOA. Heterogeneity was evaluated by Cochran’s Q and I2 tests. When P < 0.05 or I2 > 50%, a random effects model was chosen, otherwise, a fixed effects model was used. Moreover, the role of CRP in different degrees of pain was also analyzed. Sensitivity analysis was performed to evaluate the strength of the meta-analysis.ResultsFourteen studies were enrolled in the meta-analysis. No difference was found between baseline CRP and CRP levels in the last follow-up period of KOA (MD = − 0.09, 95% CI: -0.30, 0.13). Pooled data showed higher CRP concentration in patients with incident KOA when compared with controls (MD = 0.33, 95% CI: 0.04, 0.63). Moreover, higher serum COMP levels were found in patients with incident KOA (MD = 1.69, 95% CI: 0.61, 2.76) Additionally, significant higher CRP concentration was observed in KOA patients with highest degree of pain (MD = 1.60, 95% CI: 0.52, 2.67).ConclusionCRP and COMP serum levels were both associated with the incidence of KOA. Patients with a higher CRP and COMP concentration might have an increased probability of developing KOA. However, higher CRP serum levels was not related with KOA progression. Furthermore, KOA patients with more pain had higher CRP concentrations.

Nicorandil and theophylline can protect experimental rats against complete Freund's adjuvant-induced rheumatoid arthritis through modulation of JAK/STAT/RANKL signaling pathway

Signaling pathways are interesting fields of study of pathogenesis and treatment trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day) and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) / RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling pathway. Four sets of experiments were performed. First, effect of test agents on normal animals was evaluated. Second, effect of test agents was evaluated on Complete Freund's Adjuvant (CFA; 0.3ml, s.c.)-induced RA to investigate anti-arthritic effect. Third, effect of test agents was evaluated on growth hormone (GH; 2mg/kg/day, s.c.)-induced stimulation of JAK/STAT/RANKL/cytokine signaling pathway to investigate the role of this signaling pathway in their anti-arthritic effect. Fourth, the effect of test agents was performed on CFA/GH-induced RA. To fulfill this purpose, serum anti-citrullinated peptide antibody (ACPA), interleukin-6 (IL-6), and cartilage oligomeric matrix protein (COMP), together with tissue JAK2, STAT3, RANKL, inducible and endothelial nitric oxide synthases (iNOS and eNOS) as well as macrophage inflammatory protein (MIP1α) were estimated using ELISA, Western blotting and PCR techniques, confirmed by a histopathological study. Test agents significantly corrected JAK2, STAT3, RANKL and IL-6 values in animals receiving GH. Additionally, test agents could correct ACPA, IL-6, COMP, JAK2, STAT3, RANKL, iNOS, eNOS and MIP1α levels compared with the respective CFA or CFA/GH controls. These results conclude that nicorandil and theophylline have good anti-arthritic effects related to modulation of JAK/STAT/RANKL signaling pathway. Further clinical trials are claimed.

Relationship between cartilage oligomeric matrix protein (COMP) and rheumatoid arthritis severity.

BackgroundSerum cartilage oligomeric matrix protein (COMP) is a non-collagen glycoprotein produced by the cartilage, synovium, tendon, and meniscus. Recent studies showed that COMP is a reliable factor for monitoring cartilage damage.ObjectiveTo determine the relationship between serum COMP concentration and the severity of rheumatoid arthritis (RA).MethodsThis cross-sectional study lasted from 2013 to 2015 at the Rheumatology Clinic of Ghaem Hospital, Mashhad, Iran. The study population consisted of eligible patients who presented to our clinic during the study period. Four groups (150 subjects) were included as early RA (50 patients), late RA (50 patients), grades II and III OA (osteoarthritis) (25 cases, 17 grade II and 8 grade III joint destruction), and healthy controls (25 individuals). These were included consecutively. Serum COMP level was assessed by sandwich ELISA technique. In addition, ESR, hs-CRP, serum RF, and anti-CCP were assayed. X-rays of the knees (in OA) and hands (in RA) were examined for the degree of joint damage/erosion using the Short Erosion Scale (SES) in RA and Kellgren-Lawrence grading in OA. Analysis of variance (ANOVA) to compare mean COMP level among the groups and ROC (Receiver Operating Characteristic) analysis to determine the diagnostic accuracy of COMP in diagnosis of late RA were used by SPSS software (ver. 20.0).ResultsMean (±SD) serum COMP levels were 18 (±10.6) U/L in early RA, 19.3 (±9.6) U/L in late RA, 10.9 (±4.5) U/L in OA, and 4.2 (±3.8) in controls; p<0.001. Serum COMP level was higher in RA and OA groups when compared to control group. Mean (±SD) SES score was 13.5 (±7.5) in early RA and 16.4 (±9.7) in late RA (p=0.093). There was a significant positive correlation between COMP level and disease severity in early RA (r=0.677, p<0.001) as well as in late RA (r=0.753, p<0.001). Serum COMP level at a concentration of 15.25 U/L had a sensitivity of 68% and specificity of 70% to discriminate late RA from early RA (area under curve= 69% (95% CI: 58% to 79%; p=0.001).ConclusionCOMP had positive significant correlation with early and late RA severity. This serum biomarker can be a useful and easy tool for monitoring of RA patients either at early or late stages of the disease.

A putative Chondroprotective role for IL-1\u03b2 and MPO in herbal treatment of experimental osteoarthritis

BackgroundHerbal treatment may have a chondroprotective and therapeutic effect on Osteoarthritis (OA). We investigated the mechanism of action of ginger and curcumin rhizomes cultivated in Egypt in treatment of OA in rat model.MethodsThirty-five albino rats were intra-articularly injected with Monosodium Iodoacetate in the knee joint. Ginger and curcumin was orally administered at doses of 200 and 400 mg/kg (F200 and F400). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), malondialdehyde (MDA), myeloperoxidase (MPO), Interleukin-1 beta (IL-1β) and superoxide dismutase activity (SOD) were measured using ELISA. The composition of the herbal formula hydro-ethanolic extract was characterized using UPLC-ESI-MS. Histopathological changes in injected joints was examined using routine histopathology. Statistical analysis was performed using one-way ANOVA.ResultsSerum levels of COMP, HA, MPO, MDA, and IL-1β were significantly decreased in F 200, F 400 and V groups when compared to OA group (P value <0.0001). On the other hand SOD levels were significantly elevated in treated groups compared to OA groups (P value <0.0001).ConclusionsThe ginger/curcumin at 1:1 had chondroprotective effect via anti-inflammatory and antioxidant effect in rat OA model. Further pharmacological and clinical studies are needed to evaluate this effect.

CORRELATION STUDY OF SERUM CALCIUM LEVELS AND SERUM CARTILAGE OLIGOMERIC MATRIX PROTEIN LEVELS IN RHEUMATOID ARTHRITIS PATIENTS IN BANDUNG, INDONESIA

Objective: This study was designed is to determine the correlation between serum calcium level and serum cartilage oligomeric matrix protein (COMP) level in Indonesian patients with rheumatoid arthritis (RA).Subjects and Methods: The subjects are patients who visit the rheumatology clinic at a government hospital in Bandung, Indonesia. Serum calcium level was determined by a complexometric method, and the serum COMP level was determined by enzyme-linked immunosorbent assay. Statistical analysis was performed with R software.Results: The serum calcium level was 82.24±44.82 mg/mL in RA patients and 99.04±60.56 mg/mL in normal controls. The serum COMP level was 843.80±35.79 ng/ml in RA patients and 830.00±48.92 ng/ml in normal controls.Conclusion: There is no correlation between serum calcium level and serum COMP levels in RA patients (p=0.967 and rho=0.006).

Acute effect of a resistance exercise session on markers of cartilage breakdown and inflammation in women with rheumatoid arthritis.

To assess the acute effect of resistance exercise (RE) on circulating biomarkers of cartilage breakdown and inflammation in women with rheumatoid arthritis (RA). Thirty-four volunteers (17 with and 17 without RA), participated in a 25 min RE session (knee extension, knee flexion, hip abduction and hip adduction) with one set of 12 repetitions at 50% of one repetition maximum (1RM) and one set of eight repetitions at 75% of 1RM. Blood samples were collected 30 and 5 min before, immediately after and 1, 2 and 24 h after the session. We used analysis of variance for repeated-measures with Bonferroni adjustments to assess differences between groups over time. In both groups we found significant changes in interleukin (IL)-1 beta (P = 0.045), IL-1 receptor antagonist (IL-1ra) (P < 0.001), IL-10 (P = 0.004), IL-6 (P < 0.001) and cartilage oligomeric matrix protein (COMP) P < 0.001) in response to exercise, but no changes in tumor necrosis factor-alpha and C-reactive protein levels. We found no differences in the responses of the two groups to the session, except for COMP levels, which are more sensitive to exercise and rest effects in RA patients. Women with and without RA have similar changes in response to a RE session in levels of inflammation biomarkers, but not of cartilage breakdown. IL-10 and IL-1ra increased after the RE session, indicating that RE may have an acute anti-inflammatory effect. Additional studies are necessary to clarify if repeated RE sessions can have long-term anti-inflammatory effects and the possible clinical repercussions of this cartilage breakdown characteristic in response to exercise in RA patients.

Cartilage Oligomeric Matrix Protein Levels in Synovial Fluid in Patients With Primary Knee Osteoarthritis And Healthy Controls: A Preliminary Comparative Analysis With Serum Cartilage Oligomeric Matrix Protein.

This study aims (i) to compare synovial fluid and serum cartilage oligomeric matrix protein levels in patients with primary knee osteoarthritis and healthy controls, (ii) compare variations of synovial fluid and serum cartilage oligomeric matrix protein levels according to sex, Kellgren-Lawrence grades, and daytime sampling, and (iii) correlate the synovial fluid and serum cartilage oligomeric matrix protein levels with age, severity of disease, and daytime sampling. One hundred and twenty-four individuals (44 males, 80 females; median age 66 years; range 42 to 87 years) were diagnosed with primary knee osteoarthritis according to the American College of Rheumatology guidelines. Additionally, 105 healthy healthy individuals (49 males, 56 females; median age 50 years; range 30 to 75 years) were included as the control group. For both groups, a thorough clinical history and physical examination were performed. Moreover, weight-bearing anteroposterior and lateral bending 30 degrees knee X-rays were collected. Cartilage oligomeric matrix protein in serum and synovial fluid was measured by enzyme-linked immunosorbent assay. Total synovial fluid cartilage oligomeric matrix protein levels were considerably higher than total serum levels for both groups. Levels of cartilage oligomeric matrix protein in synovial fluid and serum were higher in patients than in controls for both sexes. However, only cartilage oligomeric matrix protein levels in synovial fluid were higher in female patients. The levels of synovial fluid cartilage oligomeric matrix protein were significantly higher when sampling after 12 pm. A positive correlation was found between synovial fluid and serum cartilage oligomeric matrix protein levels, age, and daytime sampling. These findings may suggest a possible role for synovial fluid and serum cartilage oligomeric matrix protein as a measure for primary knee osteoarthritis. However, more studies need to be performed to address other factors that may influence the levels of cartilage oligomeric matrix protein in synovial fluid and serum.

Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity.

The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p=0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r=0.299, p=0.010), disease duration (r=0.439, p=<0.05) and mean left KCT (r=-0.285, p=0.014) in RA. The correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r=0.372, p=0.003) and C-reactive protein (CRP) (r=0.305, p=0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.

Changes in Cartilage Biomarker Levels During a Transcontinental Multistage Footrace Over 4486 km

Background: Cartilage turnover and load-induced tissue changes are frequently assessed by quantifying concentrations of cartilage biomarkers in serum. To date, information on the effects of ultramarathon running on articular cartilage is scarce. Hypothesis: Serum concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)–1, MMP-3, MMP-9, COL2-3/4C long mono (C2C), procollagen type II C-terminal propeptide (CPII), and C2C:CPII will increase throughout a multistage ultramarathon. Study Design: Descriptive laboratory study. Methods: Blood samples were collected from 36 runners (4 female; mean age, 49.0 ± 10.7 years; mean body mass index, 23.1 ± 2.3 kg/m2 [start] and 21.4 ± 1.9 kg/m2 [finish]) before (t0) and during (t1: 1002 km; t2: 2132 km; t3: 3234 km; t4: 4039 km) a 4486-km multistage ultramarathon. Serum COMP, MMP-1, MMP-3, MMP-9, C2C, and CPII levels were assessed using commercial enzyme-linked immunosorbent assays. Linear mixed models were used to detect significant changes in serum biomarker levels over time with the time-varying covariates of body weight, running speed, and daily running time. Results: Serum concentrations of COMP, MMP-9, and MMP-3 changed significantly throughout the multistage ultramarathon. On average, concentrations increased during the first measurement interval (MI1: t1-t0) by 22.5% for COMP (95% CI, 0.29-0.71 ng/mL), 22.3% for MMP-3 (95% CI, 0.24-15.37 ng/mL), and 95.6% for MMP-9 (95% CI, 81.7-414.5 ng/mL) and remained stable throughout MI2, MI3, and MI4. Serum concentrations of MMP-1, C2C, CPII, and C2C:CPII did not change significantly throughout the multistage ultramarathon. Changes in MMP-3 were statistically associated with changes in COMP throughout the ultramarathon race (MMP-3: Wald Z = 3.476, P = .001). Conclusion: Elevated COMP levels indicate increased COMP turnover in response to extreme running, and the association between load-induced changes in MMP-3 and changes in COMP suggests the possibility that MMP-3 may be involved in the degradation of COMP. Clinical Relevance: These results suggest that articular cartilage is able to adapt even to extreme physical activity, possibly explaining why the risk of degenerative joint disease is not elevated in the running population.

Does long term colchicine prevent degradation of collagen fiber network in osteoarthritis?

Several studies have shown that colchicine exhibits an improvement in the symptoms of knee osteoarthritis (OA) but its effect on disease progression is unknown. To clarify the mechanism of action this study was done to see if colchicine prevents degradation of collagen fiber network in OA by studying serum cartilage oligomeric matrix protein (COMP) levels, a marker of cartilage turnover, over a period of 1 year. Seventy-five patients received colchicine plus paracetamol and 75 received placebo alone for the same time period. Serum COMP assays were done at baseline, 2 months and 1 year by enzyme-linked immunosorbent assay. These markers were compared between visits using repeated measures analysis of variance. Serum COMP levels in the paracetamol-alone group did not show significant change between baseline and 2 months; however, there was a significant increase in serum COMP levels from 2 months to 1 year, suggesting increased uncoupling of proteoglycans from collagen and disease progression. No such change was seen in the colchicine group, signifying lack of progression of disease in this group. Colchicine may act as a disease-modifying agent in OA.

Altered serum level of cartilage oligomeric matrix protein and its association with coronary calcification in patients with coronary heart disease.

BackgroundCartilage oligomeric matrix protein (COMP) is mainly found in the skeletal system and vascular smooth muscle cells. Recent researches showed that it had a protective function on blood vessels and could also inhibit vascular calcification. We investigated the serum COMPs in coronary heart disease (CHD) patients, and the relationship between serum COMP and the calcification of coronary artery.MethodsA total of 233 consecutive chest pain patients who first underwent coronary angiography followed by multi-slice computed tomography (MSCT) within six months were recruited and divided into two groups according to the coronary angiography luminal diameter narrowing percentages: CHD group (diameter narrowing ≥ 50%, n = 194) and control group (diameter narrowing < 50%, n = 39). The Gensini score, Syntax score and coronary artery calcium score (CACs) were calculated. The serum COMP level was determined using ELISA.ResultsThe levels of COMP were significantly higher in the CHD group than in the control group 155.7 (124.5–194.5) ng/mL vs. 128.4 (113.0–159.9) ng/mL, P = 0.019. There were no correlation between COMP, Gensini score, Syntax score, severity of coronary stenosis and the number of coronary artery with stenosis > 50%. The serum COMP was correlated with age (r = 0.294, P < 0.001), fasting glucose (r = 0.163, P = 0.015), HbA1c (r = 0.194, P = 0.015) and CACs (r = 0.137, P = 0.037). Stepwise linear regression analysis showed that COMP level and age were independent predictors of CACs in the CHD patients (β = 0.402, t = 2.612, P = 0.015; β = 0.472, t = 3.077, P = 0.005). Performance of COMP for predicting CHD was shown as area under curve (AUC): 0.632, 95% CI: 0.549–0.715 and upper tertile CACs was AUC: 0.602, 95% CI: 0.526–0.678 in receiver operating characteristic (ROC) curve analysis.ConclusionCalcification of coronary artery was an independent predictor of serum COMPs.

Serum Glycoproteome Profiles for Distinguishing Intestinal Fibrosis from Inflammation in Crohn's Disease.

BackgroundReliable identification and quantitation of intestinal fibrosis in the setting of co-existing inflammation due to Crohn’s disease (CD) is difficult. We aimed to identify serum biomarkers which distinguish inflammatory from fibrostenotic phenotypes of CD using serum glycoproteome profiles.MethodsSubjects with fibrostenotic and inflammation-predominant CD phenotypes (n = 20 per group) underwent comparison by quantitative serum glycoproteome profiles as part of a single tertiary care center cohort study. Following lectin elution, glycoproteins underwent liquid chromatography followed by tandem mass spectrometry. Identified candidate biomarkers of fibrosis were also measured by serum ELISA, a widely available technique.ResultsFive (5) glycoproteins demonstrated a ≥20% relative abundance change in ≥80% of subjects, including cartilage oligomeric matrix protein (COMP) and hepatocyte growth factor activator (HGFA). COMP (431.7±112.7 vs. 348.7±90.5 ng/mL, p = 0.012) and HGFA (152.7±66.5 vs. 107.1±38.7 ng/mL, p = 0.031) serum levels were elevated in the fibrostenotic vs. inflammatory CD groups using ELISA. Within the fibrostenotic group, intra-individual changes of candidate biomarkers revealed HGFA levels significantly declined following the resection of all diseased intestine (152.7±66.5 vs. 107.1±38.7 ng/mL, p = 0.015); COMP levels were unchanged. Immunohistochemical staining confirmed the presence of COMP in the submucosa and muscularis of resected fibrostenotic tissue.ConclusionsIn this biomarker discovery study, several serum glycoproteins, specifically COMP and HGFA, differ between between predominately inflammatory and fibrostenotic CD phenotypes. The development of blood-based biomarkers of fibrosis would provide an important complement to existing prognostic tools in IBD, aiding decisions on therapeutic intensity and mechanism selection, surgery, and the monitoring of future anti-fibrotic therapies for CD.

COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis

Background & aimsRecently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, we assessed whether serum COMP levels can be used as a non-invasive fibrosis marker in patients with chronic viral hepatitis (CVH) and compared this marker with standard methods for disease stage assessment [histology, transient elastography (TE), APRI, FIB-4]. MethodsSera from 116 CVH patients, 66 HBV [24 female; median age 53(22–76)] and 50 HCV [21 female; median age 48.5(25–69)] were investigated by COMP-ELISA. APRI and FIB-4 score was calculated in all along with TE. Liver biopsy was performed in 61. Patients were divided into two groups (F1/F2 and F3/F4) according to Metavir score. Results55/116 (47%) CVH patients were classified in F3/F4-group according to TE [14.3(9.3–75)kPa]. APRI score was >1.5 in 21/116 and FIB-4>3.25 in 20/116. Liver histology revealed 24/61 (39%) patients with significant fibrosis (stage 3–4), while 12/61 (19.7%) had cirrhosis. COMP levels correlated with TE measurements (r=0.5; p<0.001) and APRI score (r=0.23; p<0.02). The diagnostic accuracy of COMP in detecting cirrhosis was as good as TE, APRI and FIB-4 index (AUC 0.884) with sensitivity and specificity of 83.3% and 83.7% (cut-off 11.5U/L). ConclusionsCOMP serum levels performed as well as TE, APRI and FIB4 score in detecting cirrhosis in CVH patients, suggesting COMP as a sensitive non-invasive, easy to perform biomarker of liver fibrosis. Further studies are needed in order to validate our findings in CVH patients.

High Level of Serum Cartilage Oligomeric Matrix Protein and Plasma Interleukin-6 Increase the Risk of Ultrasound-detected Synovial Inflammation in Knee Osteoarthritis

Background: Inflammation of the synovial membrane involved in knee osteoarthritis (OA) pathomechanism. Cartilage oligomeric matrix protein (COMP) is a cartilage degradation product that has been considered as a biomarker of OA. Interleukin-6 (IL-6) is an inflammatory mediator involved in the pathogenesis of synovial inflammation in knee OA. this study was conducted to proof whether high level of serum COMP and plasma IL-6 increase the risk of synovial inflammation in knee OA. Methods: This was a case control study to proof about the risk of synovial inflammation in primary knee OA patients who were exposed by high level of circulating serum COMP and plasma IL-6. Every case was matched with his/ her control using pair by pair method (pair-matched). Research data was analyzed using statistic computer software program. Results: There were 56 subjects in case group and 56 subjects in control group. Bivariate analysis found that serum level of COMP gave risk for having synovial inflammation 5.5 times higher than control group (p&lt;0.001). High level of plasma IL-6 which gave risk of synovial inflammation 2.88 times higher than control group (p&lt;0.05). Multivariate analysis found that high level of serum COMP and plasma IL-6 was still significantly increased the risk factors for the development of synovial inflammation in knee OA (adjusted-OR= 3, p&lt;0.05 for high level of serum COMP; and adjusted-OR=2.7, p&lt;0.05 for high level of plasma IL-6). Conclusion: High level of serum COMP and also high level of plasma IL-6 is proven increasing the risk of synovial inflammation in knee OA.

Decreased Plasma COMP and Increased Plasma CTX-II Levels in a Chinese Pseudoachondroplasia Family with Novel COMP Mutation.

Pseudoachondroplasia (PSACH) is an autosomal dominant osteochondrodysplasia caused by mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Accurate clinical diagnosis of PSACH is sometimes difficult. Here, we identified a novel COMP mutation (c.1675G>A, p.Glu559Lys) in a Chinese PSACH family. We detected the plasma levels of COMP and type II collagen (CTX-II) in the four affected individuals. The results showed the levels of plasma COMP significantly decreased and plasma CTX-II significantly increased in the three PSACH patients with COMP mutation. However, both plasma levels of COMP and CTX-II were not to have found significant difference between the presymptomatic carrier and the age-matched subjects. In vitro analysis and immunofluorescence displayed wild type COMP homogenously expressed in cytoplasm, but mutant proteins were irregularly accumulated inside the HEK-293 cells. Western blot revealed that the quantity of the mutant COMP was more compared to wild type COMP in cells after transfection for 12 hours and 24 hours. Subsequently, 3D structural analysis showed three changes have taken place in secondary structure of the mutant COMP. In conclusion, the novel mutation of COMP may result in intracellular accumulation of the mutant protein. Decreased plasma COMP and increased plasma CTX-II may potentially serve as diagnostic markers of PSACH but may not be applicable in the presymptomatic carrier.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis.

AIMTo determine the role of cartilage oligomeric matrix protein (COMP), interleukin (IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis (OA) in postmenopausal women with estrogen deficiency.METHODSCase-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay (ELISA).RESULTSFrom 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk (OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA (cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk (OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6 (cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA (OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10 (cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk (OR = 3.4; 95%CI: 1.204-11.787; P = 0.011) for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level (cut-off point 0.364).CONCLUSIONHigh ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

Concentrations of synovial fluid biomarkers and the prediction of knee osteoarthritis 16years after anterior cruciate ligament injury.

To describe the longitudinal patterns of release, and investigate the association between a set of synovial fluid biomarkers at the acute and chronic stage and the development of radiographic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) injury. Synovial fluid was aspirated from the acutely ACL-injured knee within the first 2weeks (acute samples), and yearly (chronic samples) up to 7.5 years after injury in 88 subjects (60% men). Non-injured subjects (n=12) were used as reference group. Aggrecan, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 in synovial fluid were quantified by immunoassays. The presence of radiographic tibiofemoral (TF) or patellofemoral (PF) OA [Kellgren and Lawrence (K&L) ≥2] was examined with weight-bearing knee radiography 16 years after the ACL injury. The average acute and chronic SF concentrations of COMP and aggrecan were elevated in comparison with the reference group (P<0.001). The levels of COMP and aggrecan clearly decreased approximately half a year after the ACL injury, and returned to reference values during the 7.5 years of follow-up. Using logistic regression analysis neither acute nor chronic concentrations of the four biomarkers were associated with the development of radiographic knee OA at the 16 year follow-up. Increased synovial fluid concentrations of aggrecan and COMP was related to knee injury, but acute and chronic synovial fluid concentrations of aggrecan, COMP, MMP-3 and TIMP-1 failed to predict knee OA 16 years after ACL injury.

Abstract 4925: Plasma levels of cartilage oligomeric matrix protein (COMP), are significantly increased in patients with colorectal cancer

Abstract Introduction: Cartilage Oligomeric Matrix Protein (COMP) is a member of the thrombospondin family of extracellular calcium-binding proteins that plays role in the assembly of extracellular matrix. COMP maintains the structural integrity of cartilage through its interaction with a number of extracellular matrix proteins. COMP has a unique binding site for Vitamin D, indicating that it may also participate in storage and delivery of cell-signaling molecules. An expression array analysis of colorectal cancer samples vs normal tissue has noted overexpression of COMP mRNA. This study was undertaken to assess preoperative blood levels of COMP in the setting of colorectal cancer(CRC). Our hypothesis is that plasma levels of COMP may be elevated due to tumor overexpression and that this protein may have potential as a diagnostic marker for colorectal cancer. Method: Patients (pts) undergoing elective colorectal resection for CRC or benign colonic pathology (BCP) that had been prospectively enrolled in an IRB approved tissue and data bank for whom adequate PreOp plasma samples were available were studied. Demographic, clinical, and pathologic data were collected. Plasma COMP levels were determined via ELISA in duplicate and are reported as median +95%CI (ng/ml). Tissue expression levels were determined in paired tumor and normal tissue samples of a subpopulation of study pts by QRT-PCR .The candidacy of COMP as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Wilcoxon/Kruskal-Wallis test was used for statistical analysis, (significance p&amp;lt;0.05). Results: A total of 151 CRC (73%colon, 27%rectal) and 73 BCP pats (Adenoma 21%, diverticulitis 57%, other 22%) were studied. The male/female ratios were similar. The CRC stage distribution was: Stage 1, 22%; Stage 2, 32%; Stage 3, 31%; and Stage 4, 15%. The median plasma COMP levels were significantly higher in the CRC pts (209.2,CI: 187.8,234) vs. the BCP pats(129.6,CI: 110.7,149.2; P = &amp;lt; 0.0001). The plasma COMP levels were significantly higher in Stage III pts. (p = 0.001) and in Stage II+III pats. (p = 0.03) compared to Stage I pts. The AUC value for the ROC curve was 0.781 (sensitivity 53%, specificity 93%). Increased expression of COMP was noted in 59% of the CRC tissue samples tested (10/17) vs. paired normal tissue samples. Conclusion: The CRC median plasma COMP level was 61% higher than the median BCP result and the Stage 3 median level 50% higher than the median Stage I level. In general, plasma COMP levels increased with advancing cancer stage. The AUC results suggest COMP may have value as a CRC prognostic marker, perhaps, in combination with other protein markers to increase the sensitivity. Tissue expression analysis suggests that the most likely source of the added COMP in the plasma is the tumor itself. Further study with larger populations of control and CRC pts is warranted. Citation Format: Hmc Shantha Kumara, Hiromichi Miyagaki, Xiaohong Yan, Linda Njoh, Vesna Cekic, Nipa D. Gandhi, Melissa M. Alvarez-Downing, Richard L. Whelan. Plasma levels of cartilage oligomeric matrix protein (COMP), are significantly increased in patients with colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4925.