Serum Cartilage Oligomeric Matrix Protein Levels Research Articles

Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration

ObjectiveIntervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship.MethodsIVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1–4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I–V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses.ResultsCOMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD.ConclusionsIncreases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.

Role of Alphacalcidol to Reduce Pain and Serum Cartilage Oligomeric Matrix Protein in Elderly with Knee Osteoarthritis

Objective : To determine the effect of Alphacalcidol supplementation on pain based on WOMAC pain index and joint cartilage condition based on cartilage oligomeric matrix protein (COMP) serum markers in knee osteoarthritis (OA) elderly patients. Materials andMethods : This is a randomized, double-blind, and placebo-controlled trial. Symptomatic knee OA elderly subjects visited our clinic in Jakarta July-December 2017 were recruited. History taking, physical examinations, and knee radiology were performed. Serum Vitamin D (25(OH)D) and COMP were analysed using chemiluminescent immunoassay and enzyme-linked immunosorbent assay, respectively. Body mass index, physical activity, sun exposure frequency, and dietary vitamin D were assessed. Subjects were randomly allocated to either intervention group to be given 1 μg Alphacalcidol or control group to be given placebo for 12 weeks. Comparation analysis of WOMAC pain index and serum COMP concentration between both groups was performed. Results : There were 146 subjects participated this study. Increases of 25(OH)D were found in intervention group (2.63 ±11.24 nmol/L, p=0.05) and control groups (1.09±9.42 nmol/L, p=0.28). Alphacalcidol significantly reduced pain based on WOMAC indicator with mean reduction differences of intervention group compared to control group was 2.174±1.060 (p=0.00). COMP serum level was reduced with mean reduction differences of intervention group compared to control group was 38.15±87.553 ng/ ml (p=0.39). Alphacalcidol and gender were the determinants of WOMAC pain index reduction (p=0.00 and p=0.06, respectively) while Alphacalcidol was the only serum COMP level change determinant (p=0.39). Conclusions :Alphacalcidol administration reduced pain based on WOMAC indicator and COMP serum in knee OA elderly subjects. Bangladesh Journal of Medical Science Vol. 21 No. 04 October’22 Page : 759-771

THE CORRELATION OF JOINT SPACE WIDTH WITH SYNOVIAL FLUID CARTILAGE OLIGOMERIC MATRIX PROTEIN LEVEL IN KNEE OSTEOARTHRITIS PATIENTS

Osteoarthritis (OA) was a degenerative joint disease associated with joint cartilage damage, where the most commonly affected joints are vertebrae, pelvis, knee, and ankle. Pathomechanism of OA includes various etiologies that play a role in the balance destruction and synthesis of cartilage. Radiology examination was the most common method used to monitor the progression of OA but can not show changes in knee OA except in the advanced phase of the disease. Conventional radiology can estimate the thickness of the cartilage through measurement joint space width (JSW). One alternative method that can detect changes in the joint at an early stage of the disease is a measurement of the synthesis and degradation markers of the tissue. Cartilage oligomeric matrix protein (COMP) was one of the cartilage destruction markers of non-aggrecan and non-collagen groups, found in cartilage and other tissues. Several studies have reported the correlation between serum or synovial fluid COMP level with the radiographic progression of knee OA patients. This study aimed to assess the correlation between joint space width and synovial fluid COMP level in knee OA subjects. The study was a descriptive-analytic method with a cross-sectional design in 69 knee OA subjects. It was conducted in the rheumatology outpatient clinic of Wahidin Sudirohusodo Hospital Makassar and its networks on March-June 2015. In this study, we found a correlation between joint space width (JSW) and synovial fluid COMP level, where synovial fluid COMP levels were higher in knee OA subjects with more severe joint space width narrowing, and it was not influenced by age and obesity

High Levels of Expression of Cartilage Oligomeric Matrix Protein in Lymph Node Metastases in Breast Cancer Are Associated with Reduced Survival.

Simple SummaryCartilage oligomeric matrix protein (COMP) is an emerging independent prognostic marker for breast cancer patients. COMP expression by cancer cells affects their metabolism, metastases, and the abundance of cancer stem cell populations. This study assessed the levels of COMP in the sera of metastatic breast cancer patients. Further, matched tumor tissues from the primary tumor and metastases were stained for COMP expression with immunohistochemistry. The levels of serum COMP were highest in the blood of metastatic ER-positive and HER2-positive patients. The expression of COMP in primary tumors correlated with COMP expression in the metastatic loci. Lymph node metastases (LNM) with COMP expression were associated with reduced survival. The expression of COMP in LNM at the time of primary diagnosis could indicate later development of visceral and lung metastases.Cartilage oligomeric matrix protein (COMP) is a regulator of the extracellular matrix and is expressed primarily in the cartilage. Recently, COMP expression was also documented in breast cancer patients both in sera and tumor biopsies, in both of which it could serve as an independent prognostic marker. This study aimed to assess COMP as a potential biomarker in the group of metastatic breast cancer patients. Levels of COMP were measured by ELISA in serum samples of 141 metastatic breast cancer patients. Biopsies from primary tumors, synchronous lymph node metastases, and distant metastases were stained for COMP expression. The levels of serum COMP were higher in patients with ER- and HER2-positive tumors when compared to triple-negative tumors and correlated with the presence of bone and lung metastases, circulating tumor cell count, and clusters. Most of the primary tumors expressing COMP (70%) retained the expression also in the lymph node metastases, which correlated with visceral metastases and reduced survival. In conclusion, COMP appears as a valuable biomarker in metastatic breast cancer patients indicating a more severe stage of the disease. Serum COMP levels were associated with specific types of metastases in patients with metastatic breast cancer emphasizing that further studies are warranted to elucidate its potential role as a monitoring marker.

Clinical, Biochemical, Radiological, Genetic and Therapeutic Analysis of Patients with COMP Gene Variants.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (MED1) are two rare skeletal disorders caused by cartilage oligomeric matrix protein (COMP) variants. This study aims to analyze the genotype and phenotype of patients with COMP variants. Clinical information for 14 probands was collected; DNA was extracted from blood for COMP variant detection. Clinical manifestations and radiology scoring systems were established to evaluate the severity of each patient's condition. Serum COMP levels in PSACH patients and healthy subjects were measured. Thirty-nine patients were included, along with 12 PSACH probands and two MED1 probands. Disproportionate short stature, waddling gait, early-onset osteoarthritis and skeletal deformities were the most common features. The height Z-score of PSACH patients correlated negatively with age at evaluation (r =  - 0.603, p = 0.01) and the clinical manifestation score (r =  - 0.556, p = 0.039). Over 50% of the PSACH patients were overweight/obese. The median serum COMP level in PSACH patients was 16.75ng/ml, which was significantly lower than that in healthy controls (98.53ng/ml; p < 0.001). The condition of MED1 patients was better than that of PSACH patients. Four novel variants of COMP were detected: c.874T>C, c.1123_1134del, c.1531G>A, and c.1576G>T. Height Z-scores and serum COMP levels were significantly lower in patients carrying mutations located in calmodulin-like domains 6, 7, and 8. As the two phenotypes overlap to different degrees, PSACH and MED1 are suggested to combine to produce "spondyloepiphyseal dysplasia, COMP type". Clinical manifestations and radiology scoring systems, serum COMP levels and genotype are important for evaluating patient condition severity.

Effect of Tongluozhitong Prescription-Assisted Intra-Articular Injection of Sodium Hyaluronate on VAS Score and Knee Lysholm Score in Patients with Knee Osteoarthritis.

Knee osteoarthritis (KOA) has become one of the leading causes of workforce loss in the middle-aged and elderly population and a global public health problem second only to cardiovascular disease, so we need to find more effective treatments for this disease. In this study, we selected 120 patients with KOA admitted to our hospital from June 2018 to December 2020 and divided them into treatment group 1, treatment group 2, and joint group according to the random number table method, with 40 patients in each group. Treatment group 1 was treated with Tongluozhitong prescription dip-soaking therapy, treatment 2 group was treated with intra-articular injection of sodium hyaluronate, and the joint group was treated with a combination of both modalities for 4 weeks in all three groups. Clinical efficacy, visual analogue scale (VAS), Lysholm knee score (LKS), activity of daily living score (ADL), the levels of bone metabolic markers such as cartilage oligomeric matrix protein (COMP), type II collagen degradation maker (CTX-II), and matrix metalloproteinase-3 (MMP-3), and the levels of inflammatory mediators such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and hypersensitive C-reactive protein (hs-CRP) were used as observations to compare and analyze the therapeutic effects of the three treatment regimens in KOA patients. The results showed that the clinical excellence rates of the joint group, treatment group 1, and treatment group 2 were 72.50%, 50.00%, and 90.00%, respectively, with statistically significant differences between any two comparisons. After treatment, VAS scores, serum COMP, CTX-II, MMP-3, IL-1β, TNF-α, and hs-CRP levels decreased in all three groups, and the levels of each index were as follows: joint group < treatment group 1 < treatment group 2, and the difference between any two comparisons was statistically significant. The LKS score and ADL score increased in all three groups, and the levels of each index were as follows: joint group > treatment group 1 > treatment group 2, with statistically significant differences in any two groups compared. None of the patients in the three groups experienced any significant adverse effects during treatment. This suggests that the dip-soaking therapy of Tongluozhitong prescription is more advantageous than intra-articular sodium hyaluronate injection treatment in suppressing the level of serum bone metabolic markers and inflammatory mediators, reducing pathological joint damage, relieving symptoms of pain, alleviating degenerative joint symptoms, and improving knee function in KOA patients. The combination of the two in KOA patients can significantly improve the efficacy and has a good safety profile.

Effects of Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate on Grip Strength, Cartilage Structure and Joint Remodelling Markers in a Rat Model of Osteoarthritis

Background: Osteoarthritis is a degenerative joint disease lacking disease-modifying therapeutic agents. This study aimed to compare the effects of palm tocotrienol-rich fraction (TRF), glucosamine sulphate, and both agents combined in rats with osteoarthritis induced by monosodium iodoacetate (MIA). Methods: Thirty adult male rats were randomized into normal control, and osteoarthritis groups were treated orally daily with vehicle, palm TRF (100 mg/kg), glucosamine sulphate (250 mg/kg), and both agents combined for 4 weeks. Body weight and grip strength were measured weekly. After being sacrificed, the joints and blood were harvested for histology and serum cartilage oligomeric matrix protein (COMP) levels. Results: The body weight of the rats receiving treatment rebounded significantly after an initial reduction (vs osteoarthritic control, p &lt; 0.05). The rats receiving combined treatments showed significantly better grip strength than the osteoarthritic control and individual treatment groups (p &lt; 0.05). The serum COMP level was lower in all the treated groups (vs osteoarthritic control, p &lt; 0.05). Cartilage histology of the treated rats was not significantly improved (vs osteoarthritic control, p &gt; 0.05). Conclusion: The combination of palm TRF and glucosamine sulphate was more effective than individual agents in improving the grip strength of the rats, but the cartilage damage might need more time to heal.

Serum cartilage oligomeric matrix protein is decreased in patients with pulmonary hypertension: a potential protective factor.

Cartilage oligomeric matrix protein (COMP) was a protective factor in the cardiovascular system. Previous studies showed that hypoxia led to decreased COMP in rat models of pulmonary hypertension. However, the expression pattern of COMP in the pulmonary hypertension population was unclear. A total of 35 patients newly diagnosed with pulmonary hypertension and 70 controls were enrolled in the study. Circulating COMP concentrations of serum samples were measured by enzyme-linked immunosorbent assay and were analyzed the association with multiple clinical variables. Serum COMP concentrations in the pulmonary hypertension group were significantly declined in comparison with age- and sex-matched normal controls, especially in the female subgroup. No significant difference of COMP concentrations was observed in the etiological classification, heart function classification, and risk stratification. Major hemodynamic parameters, six-minute walk distance, N-terminal pro brain natriuretic peptide, and short-term prognosis were not statistically associated with COMP. However, some echocardiography parameters, like tricuspid annular plane systolic excursion and mean right atrial pressure, were found the negative relation to COMP concentrations. In conclusion, serum COMP levels were decreased in the patients with pulmonary hypertension, which was in accordance with its known biological effects. Its association with long-term prognosis was worth further exploring.

Serum Cartilage Oligomeric Matrix Protein Detects Early Osteoarthritis in Patients With Anterior Cruciate Ligament Deficiency

To investigate the ability of serum cartilage oligomeric matrix protein (COMP) to detect early osteoarthritis (OA) (International Cartilage Research Society [ICRS] grade 1 or 2 cartilage lesions) in patients with anterior cruciate ligament (ACL)-deficient patients. Patients with an ACL injury of Kellgren-Lawrence grade 0 or 1 were enrolled. Serum samples for COMP measurement were obtained before surgery. The cartilage surfaces of 6 compartments were classified using the ICRS grading system. The patients were divided into groups with and without early OA according to the cartilage findings and diagnostic criteria for early OA. In total, 98 patients (mean age 23.7 years; range 12 to 49) were included, with 30 patients (30.6%) in the early OA group and 68 (69.4%) in the no early OA group. The 2 groups significantly differed in age, body mass index, preoperative Tegner activity scale, and serum COMP level. The cutoff value of serum COMP for the presence of early OA arthroscopic cartilage lesions was 152.0 ng/mL. Multiple logistic regression analysis revealed age (odds ratio 1.09; 95% confidence interval [CI] 1.02 to 1.16; P= .01) and serum COMP (odds ratio 1.02; 95% CI 1.01 to 1.04; P < .001) to be independent factors for the presence of early OA arthroscopic cartilage findings. The incidence of early OA arthroscopic cartilage findings was ∼30% in patients with ACL deficiency, and serum COMP levels were significantly higher in the early OA group than in the no early OA group. The optimum cutoff value for serum COMP was 152 ng/mL. Serum COMP can be used to detect early cartilage change in patients with ACL deficiency. Ⅲ, retrospective comparative study.

Serum cartilage oligomeric matrix protein is correlated with quantitative magnetic resonance imaging and arthroscopic cartilage findings in anterior cruciate ligament deficient knees without osteoarthritic changes.

To investigate the association between serum biomarker [cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3)] levels and clinical, magnetic resonance imaging (MRI), and arthroscopic findings in anterior cruciate ligament (ACL)-deficient knees without osteoarthritic changes on radiographs. Patients with ACL injury of Kellgren-Lawrence grade 0 or 1 were enrolled. Serum COMP and MMP-3 levels were measured preoperatively. Correlations of serum biomarker levels with age, body mass index (BMI), duration from time of injury, Tegner activity scale (TAS) score, Lysholm knee score, International Knee Documentation Committee score, KT-1000 arthrometer measurements, whole-organ MRI score (WORMS), MRI T2 relaxation time, and arthroscopic International Cartilage Research Society (ICRS) grade were assessed by calculating Spearman correlation coefficients. Associations between intraoperative findings (cartilage, meniscus) and serum biomarker levels were determined using the Mann-Whitney U test. Multiple regression analysis was performed to investigate the correlations between serum biomarker levels and MRI and arthroscopic findings. Ninety-eight patients with a mean age of 23.7 years were enrolled. Higher serum COMP level was correlated with older age and higher BMI, TAS score, serum MMP-3 level, WORMS, and T2 relaxation times (medial femur, medial tibia). Multivariate analysis showed that the serum COMP level was independently associated with WORMS and ICRS grade. The serum COMP level was correlated with age, BMI, TAS score, and MMP-3 level in ACL-deficient knees and was independently correlated with WORMS and ICRS grade. Thus, the serum COMP level can help detect cartilage degeneration even in patients without radiographic osteoarthritic changes. Key Points • Serum COMP correlated with WORMS and ICRS grade in ACL deficient knee. • The serum COMP level could help in detecting cartilage degeneration, even in patients with no radiographic osteoarthritic changes.

Correlation between serum cartilage oligomeric matrix protein and major adverse cardiovascular events within 30 days in patients with acute coronary syndrome.

BackgroundWe studied the correlation between cartilage oligomeric matrix protein (COMP) and major adverse cardiovascular events in patients with acute coronary syndrome (ACS) within 30 days.MethodsThis study included 170 ACS patients who were hospitalized in the Second Affiliated Hospital of Nantong University from August 2017 to April 2019. Serum COMP level was measured at baseline. The enrolled patients were followed up for 30 days and grouped according to the occurrence of major adverse cardiovascular events (MACE) during follow-up. Among the 170 patients, 23 patients had MACE during hospitalization (MACE group), and 147 patients had no MACE (no MACE group).ResultsThe serum COMP levels in the MACE group were significantly higher than those of the non-MACE group [84.85 (51.55, 141.75) vs. 20.65 (9.11, 46.31) ng/mL, respectively, P<0.05]. The area under the receiver operating characteristic (ROC) curve for COMP in predicting the occurrence of MACE within 30 days was 0.839, with a cutoff level of 39.9 ng/mL [95% confidence interval (CI): 0.774–0.890], 86.96% sensitivity, and 72.79% specificity (P<0.0001). Multivariate logistic regression analysis showed that serum COMP could be used as an independent predictor of MACE within 30 days in ACS patients [odds ratio (OR): 1.024, 95% CI: 1.0133–1.0349, P=0.0001].ConclusionsSerum COMP is associated with the short-term prognosis of ACS patients. High serum COMP levels can be used as a predictor of MACE within 30 days in ACS patients.

Study of serum traditional and nontraditional biomarkers in Rheumatoid arthritis patients

The study of biomarkers in Rheumatoid arthritis (RA) is highly indispensable to understand mechanisms of pathogenesis, diagnosis, prognosis, and treatment of disease. The role of traditional biomarkers like Anti-CCP, RF, and inflammatory markers like ESR and CRP is well established. In this study, we aimed to measure nontraditional biomarkers like Hyaluronic acid (HA), Cartilage oligomeric matrix protein (COMP), and Osteocalcin in the serum of RA patients and also to establish an association with traditional markers. It was a cross-sectional study involving 152 RA patients based on the 1987 ACR criteria for the diagnosis of RA and 68 age‑ and sex-matched healthy controls. After the clinical examination, traditional markers were assessed to measure the disease activity along with non traditional markers in RA patients. All the values were expressed as median (25th–75th percentile). In our study, there was a significant increase in serum HA levels in RA patients compared to healthy controls (p  &lt; 0.03), whereas no significant difference in serum COMP and osteocalcin levels. The traditional inflammatory markers were significantly increased in RA patients than controls with (p  &lt; 0.001). The serum HA levels were significantly correlated with traditional markers in RA patients. Conclusion: Significant increase in serum HA level in RA patients indicating synovial inflammation, but there were no notable changes in COMP and osteocalcin level in serum presuming the combination of these markers may be useful along with traditional markers in the different stages of RA.

Short-term Response of Serum Cartilage Oligomeric Matrix Protein to Different Types of Impact Loading Under Normal and Artificial Gravity.

Microgravity during long-term space flights induces degeneration of articular cartilage. Artificial gravity through centrifugation combined with exercise has been suggested as a potential countermeasure for musculoskeletal degeneration. The purpose of this study was to investigate the effect of different types of impact loading under normal and artificial gravity conditions on serum concentrations of cartilage oligomeric matrix protein (COMP), a biomarker of cartilage metabolism. Fifteen healthy male adults (26 ± 4 years, 181 ± 4 cm, 77 ± 6 kg) performed four different 30-min impact loading protocols on four experimental days: jumping with artificial gravity elicited by centrifugation in a short-arm centrifuge (AGJ), jumping with artificial gravity generated by low-pressure cylinders in a sledge jump system (SJS), vertical jumping under Earth gravity (EGJ), and running under Earth gravity (RUN). Five blood samples per protocol were taken: 30 min before, immediately before, immediately after, 30 min after, and 60 min after impact loading. Serum COMP concentrations were analyzed in these samples. During the impact exercises, ground reaction forces were recorded. Peak ground reaction forces were significantly different between the three jumping protocols (p < 0.001), increasing from AGJ (14 N/kg) to SJS (22 N/kg) to EGJ (29 N/kg) but were similar in RUN (22 N/kg) compared to SJS. The serum COMP concentration was increased (p < 0.001) immediately after all loading protocols, and then decreased (p < 0.001) at 30 min post-exercise compared to immediately after the exercise. Jumping and running under Earth gravity (EGJ and RUN) resulted in a significantly higher (p < 0.05) increase of serum COMP levels 30 min after impact loading compared to the impact loading under artificial gravity (RUN +30%, EGJ +20%, AGJ +17%, and SJS +13% compared to baseline). In conclusion, both the amplitude and the number of the impacts contribute to inducing higher COMP responses and are therefore likely important factors affecting cartilage metabolism. RUN had the largest effect on serum COMP concentration, presumably due to the high number of impacts, which was 10 times higher than for the jump modalities. Future studies should aim at establishing a dose-response relationship for different types of exercise using comparable amounts of impacts.

Metabolic Syndrome and Its Effects on Cartilage Degeneration vs Regeneration: A Pilot Study Using Osteoarthritis Biomarkers.

Osteoarthritis (OA) of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level. After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic (MetS) OA and non-metabolic (Non-MetS) OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III (NCEP-ATP-III) criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein (COMP) and Procollagen type IIA N terminal Propeptide (PIIANP) levels were used as tools to assess cartilage degeneration and regeneration, respectively. 22 among 41 patients (53.66%) had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence (KL) grades were comparable in both groups. MetS-OA group showed significant increase in serum COMP levels (p = 0.03) with no significant effect on serum PIIANP levels (p = 0.46). Hypertriglyceridemia showed independent association with both cartilage anabolism (p = 0.03) and catabolism (p = 0.03). Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.

Elevated serum cartilage oligomeric matrix protein and the metalloproteinase‐ADAMTS7 levels are associated with vascular calcification in maintenance hemodialysis patients

Vascular calcification is common in maintenance hemodialysis (HD) patients. Recent studies showed that cartilage oligomeric matrix protein (COMP) could protect blood vessels fromcalcification, but the role of ADAMTS7 was opposite. We aimed to investigate the relationship between serum COMP, ADAMTS7 levels and vascular calcification scores in HD patients. Serum COMP and ADAMTS7 levels were tested by ELISA and we compared calcification scores between high and low COMP groups, also between high and low ADAMTS7 groups. We also investigated the differences of serum COMP and ADAMTS7 levels between mild and severe vascular calcification groups. The relationship between serum COMP and ADAMTS7 levels was analyzed in the end. Serum COMP and ADAMTS7 levels were both higher in HD patients than in control (29.63 vs 14.23ng/mL, P=.002, 11.12 vs 2.40ng/mL, P=.005). Serum COMP levels in severe vascular calcification (VC) group were higher than in mild VC (43.13±28.77 vs 26.75±18.22ng/mL, P=.010). Serum ADAMTS7 levels were positively correlated with radial and digital arteries (small arteries) calcification scores (r=.249, P=.033). And serum COMP and ADAMTS7 levels were positively correlated (r=.348, P=.026). Serum COMP and ADAMTS7 levels were probably associated with vascular calcification scores in HD respectively.

Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment.

PurposeDapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance.MethodsDH-TENV formulations were prepared using an injection- sonication method and optimized using a 33 Box-Behnken-design with Design Expert® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed.ResultsThe optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid.ConclusionThe results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.

Association between serum cartilage oligomeric matrix protein and coronary artery calcification in maintenance hemodialysis patients.

BackgroundCoronary artery calcification (CAC) is common in end-stage renal disease (ESRD) patients, and the extent of CAC is closely related to cardiovascular outcomes in ESRD patients. Cartilage oligomeric matrix protein (COMP), as a component of the vascular matrix, has been found to be an inhibitor of arterial calcification in basic studies. However, there is no clinical research on the correlation between COMP and CAC in maintenance hemodialysis (MHD) patients. The aim of this study was to explore the relationship between serum COMP levels and CAC and cardiovascular events in MHD patients.MethodsSerum COMP levels were compared between 54 MHD patients and 66 healthy people. MHD patients were then divided into three groups according to the tertiles of the concentration of COMP level and were followed up for major adverse cardiac events (MACEs), which were defined as a combined end point of new onset angina pectoris, nonfatal myocardial infarction, heart failure, coronary artery revascularization, hospitalization due to angina pectoris and all-cause deaths. The CAC score was calculated based on computed tomography scans.ResultsThe serum COMP level in MHD patients was significantly higher than that in the general population [984.23 (248.43–1902.61) ng/mL vs. 219.01 (97.26–821.92) ng/mL, P < 0.01]. Serum COMP levels were positively correlated with CAC (r = 0.313, P = 0.021) and serum parathyroid hormone in MHD patients (r = 0.359, P < 0.01). Linear regression suggested that after adjusting for age, fasting blood glucose (Glu) and glycosylated hemoglobin (HbAlc), CAC score was an independent predictor in the final model for COMP level (β = 0.424, t = 3.130, P < 0.01). The receiver operating characteristic (ROC) curve showed that COMP ≥ 994 mg/mL had 68.0% sensitivity and 72.4% specificity for the prediction of severe CAC [area under the curve (AUC): 0.674, P = 0.030, 95% CI: 0.526–0.882]. After a median follow-up of 16 months (8–24 months), there was no difference in the incidence rate of MACEs between the upper, middle and lower serum COMP groups.ConclusionsOur study found that MHD patients have higher levels of circulating COMP than controls. The serum COMP level is positively correlated with CAC score and could be used as a biomarker of severe CAC in MHD patients. However, there is no obvious correlation between serum COMP levels and the incidence of cardiovascular events.

Effect of Peat Intervention on Pain and Gait in Patients with Knee Osteoarthritis: A Prospective, Double-Blind, Randomized, Controlled Study.

Methods Knee osteoarthritis patients with Visual Analog Scale (VAS) of 3 or more and Kellgren–Lawrence osteoarthritis grades 1 to 3 were included. Patients with history of intraarticular injection treatment were excluded. Forty-one participants were randomly allocated to the peat intervention group (n = 22) or the hot-pack-only control group (n = 19). Peat and hot pack were applied to both knees of each group of patients. Each intervention session lasted 20 minutes, and eight sessions were completed over five days. VAS, serum cartilage oligomeric matrix protein (COMP), and gait parameters were evaluated before and after the whole interventions. Results VAS in the peat group decreased from 6.000 to 3.409 after intervention (p < 0.001) and also decreased in the control group from 5.737 to 4.421 (p < 0.001). VAS score reduction between two periods was greater in the peat group than that in the control group (p < 0.001). There was no significant difference in the serum COMP level in either intergroup or intragroup analysis. In gait analysis, the gait velocity of the peat group increased from 0.781 m/s to 0.873 m/s after intervention (p=0.002), while it decreased in the control group. The knee varus/valgus range of motion during gaits was reduced from 11.455° to 8.439° after intervention in the peat group (p=0.006). Conclusions This study showed that peat can be considered as a therapeutic option for pain relief of knee osteoarthritis patients. The reduction in knee joint varus/valgus range of motion and the increase in gait velocity after peat intervention were also identified through this research, which is the first to analyze the effects of peat on gait.

Impact of knee joint loading on fragmentation of serum cartilage oligomeric matrix protein.

The aim of the study was to examine the effect of mechanical knee joint loading on the fragmentation pattern of serum cartilage oligomeric matrix protein (COMP). Ten healthy men ran with knee orthoses that were passive or active (+30.9 N·m external flexion moments) on a treadmill (30 minute; v = 2.2 m/s). Lower-limb mechanics, serum COMP levels, and fragmentation patterns (baseline; 0, 0.5, 1, 2 hours postrunning) were analyzed. Running with active orthoses enhanced knee flexion moments, ankle dorsiflexion, and knee flexion angles (P < .05). There was an increase in serum COMP (+25%; pre: 8.9 ± 2.4 U/l; post: 10.7 ± 1.9 U/l, P = .001), COMP pentamer/tetramer (+88%; 1.88 ± 0.81, P = .007), trimer (+209%; 3.09 ± 2.65, P = .005), and monomer (+78%; 1.78 ± 0.85, P = .007) after running with passive orthoses and in serum COMP (+41%; pre: 8.5 ± 2.7 U/l; post: 11.3 ± 2.1 U/l, P < .001), COMP pentamer/tetramer (+57%; 1.57 ± 0.39, P = .007), trimer (+86%; 1.86 ± 0.47, P = .005), and monomer (+19%; 1.19 ± 0.34, P = .114) after running with active orthoses. Increased fragmentation might indicate COMP release from cartilage while running. Interestingly, 0.5 h up to 2 hours after running with passive orthoses, trimer (0.5 hour: 2.73 ± 3.40, P = .029; 2 hours: 2.33 ± 2.88, P = .037), and monomer (0.5 hour: 2.23 ± 2.33, P = .007; 1 hour: 2.55 ± 1.96, P = .012; 2 hours: 2.65 ± 2.50, P = .009) increased while after running with active orthoses, pentamer/tetramer (1 hour: 0.79 ± 0.28, P = .029), and trimer (1 hour: 0.63 ± 0.14, P = .005; 2 hours: 0.68 ± 0.34, P = .047) decreased. It seems that COMP degradation and clearance vary depending on joint loading characteristics.

Associations between suprapatellar pouch effusion-synovitis, serum cartilage oligomeric matrix protein, high sensitivity C-reaction protein, knee symptom, and joint structural changes in patients with knee osteoarthritis.

To investigate the cross-sectional associations between suprapatellar pouch effusion-synovitis and serum levels of cartilage oligomeric matrix protein (COMP), high sensitivity C-reaction protein (hs-CRP), knee symptom, and structural changes in patients with symptomatic knee osteoarthritis (OA). A total of 173 subjects were included. The osteophytes, joint space narrowing (JSN), and radiographic severity of OA were determined using X-ray. Cartilage defects, bone marrow lesions (BMLs), and suprapatellar pouch effusion-synovitis were assessed using magnetic resonance imaging. Serum levels of COMP and hs-CRP were measured by enzyme-linked immunosorbent assay. The knee joint symptom was self-reported using visual analogue scale. In this OA cohort, after adjustment for age, sex, and BMI, the presence of pathological effusion-synovitis was associated with serum levels of COMP (β: 30.98, P = 0.018), and suprapatellar pouch effusion-synovitis maximum areas were associated with serum hs-CRP levels. Both suprapatellar pouch effusion-synovitis maximum area and grade were associated with osteophytes and Kellgren-Lawrence scores (ORs: 1.29-1.54, all P < 0.05). In patients with high tertile of hs-CRP, both suprapatellar pouch effusion-synovitis maximum area and grade were associated with cartilage defects at lateral and medial tibiofemoral sites (ORs: 3.01-8.41, all P < 0.05) after adjustment for covariates. In female patients, the significant associations were present between suprapatellar pouch effusion-synovitis and medial tibiofemoral BMLs (ORs: 1.43-1.53, all P < 0.05) after adjustment for covariates. Suprapatellar pouch effusion-synovitis was associated with serum levels of COMP as well as hs-CRP and knee structural abnormalities in patients with knee OA. These suggested that effusion-synovitis may play a role in knee OA.Key Points• Suprapatellar pouch effusion-synovitis is associated with serum levels of COMP in patients with knee OA.• Suprapatellar pouch effusion-synovitis is associated with cartilage defects in knee OA patients with high systemic inflammation.