Serum Cartilage Oligomeric Matrix Protein Research Articles

Association between osteoarthritis-related serum biochemical markers over 10-13 years and knee symptoms in middle-aged adults.

To describe the associations between OA-related biochemical markers and knee symptoms in middle-aged adults followed up over 10-13 years. Blood samples were collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year: 2004-06) and 10-13 year follow-up at CDAH-3. Serum samples from baseline (n=156) and follow-up (n=167) were analyzed for three OA-related biomarkers [cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-3, and hyaluronan (HA)] using non-isotopic enzyme-linked immunosorbent assay (ELISA). Knee symptoms were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale at follow-up. Univariable and multivariable (adjusted for age, sex, and body mass index (BMI)) zero-inflated Poisson (ZIP) regression models were used for analysis. In cross-sectional multivariable models, significant positive associations between COMP [ratio of means (RoM): 1.156; 95%CI: 0.989, 1.324], MMP-3 [RoM: 1.013; 95%CI: 1.001, 1.025], and HA [RoM: 1.008; 95%CI: 1.002, 1.015] with knee pain and WOMAC-total score were observed in middle-aged adults. Baseline serum MMP-3 [RoM: 1.013; 95%CI: 1.006, 1.020], sum of serum COMP [RoM: 1.022; 95%CI: 1.011, 1.033], and an increase in the serum HA [RoM: 1.014; 95%CI:1.007, 1.020] were significantly positively associated with knee pain assessed after 10-13 years. The cumulative COMP levels in young adulthood (baseline) and mid-adulthood (follow-up), MMP-3 levels in young adulthood (baseline), and change in HA levels over the follow-up period were positively associated with knee pain assessed after 10-13 years. These biochemical markers measured in middle-aged adults may be explored further as a predictor of future knee symptoms.

Effect of older age and/or ACL injury on the dose–response relationship between ambulatory load magnitude and immediate load-induced change in serum cartilage oligomeric matrix protein

PurposeThis study aimed to assess the influence of older vs. younger age and previous anterior cruciate ligament (ACL) injury on resting serum cartilage oligomeric matrix protein (sCOMP[tpre]) concentration, on immediate load-induced sCOMP kinetics after a 30-min treadmill walking stress (∆_sCOMP[tpost]), and on the dose–response relationship between ambulatory load magnitude and ∆_sCOMP(tpost). MethodsA total of 85 participants were recruited in 4 groups (20–30 years: 24 healthy, 23 ACL-injured; 40–60 years: 23 healthy, 15 ACL-injured). Blood samples were collected immediately before and after a walking stress at 80%, 100%, or 120% bodyweight (BW) on 3 test days and analyzed for sCOMP concentration. Linear models were used to estimate the effect of age, knee status (unilateral ACL injury, 2–10 years prior), and sex on sCOMP(tpre), ∆_sCOMP(tpost)), and the dose–response between ambulatory load magnitude and ∆_sCOMP(tpost). ResultsWe found that sCOMP(tpre) was 21% higher in older than younger participants (p < 0.001) but did not differ between ACL-injured and healthy participants (p = 0.632). Also, ∆_sCOMP(tpost) was 19% lower in older than younger participants (p = 0.030) and increased with body mass index (p < 0.001), sCOMP(tpre) (p = 0.008), and with 120%BW (p < 0.001), independent of age, ACL injury, or sex. ConclusionAge but not prior ACL injury influences resting sCOMP and load-induced sCOMP. The dose–response relationship between ambulatory load magnitude and load-induced sCOMP changes is not affected by age, ACL injury, or sex. A better understanding of systemic sCOMP and the role of its mechanoresponse for the understanding of osteoarthritis pathophysiology and monitoring intervention efficacy may require knowledge of individual cartilage composition and tissue-level loading parameters.

Analysis and study on biomarkers of local muscle fatigue caused by repetitive lifting task

BackgroundWork-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators.MethodsThirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data.ResultsBoth subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p < 0.05). There was a certain degree of correlation between the markers with statistical differences before and after fatigue.ConclusionsMetabolic markers (serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+) and pain markers (serum NPY) can reflect local muscle fatigue to a certain extent in repetitive manual lifting tasks. It is necessary to further expand the research on fatigue-related biomarkers in different types of subjects and jobs in the future.

Metformin as adjuvant therapy in obese knee osteoarthritis patients

AimsThis study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects.Patients and methodsIn this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1β) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks.ResultsFollowing a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1β in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively).ConclusionMetformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1β levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores.Clinicaltrials.gov IDNCT05638893/Registered December 6, 2022 — Retrospectively.

Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis.

This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry. COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that COMP mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative COMP mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, COMP mRNA expression was considerably up-regulated in a time-dependent manner. All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.

Interactions of cumulative load with biomarkers of cartilage turnover predict knee cartilage change over 2 years: data from the osteoarthritis initiative.

The purpose was to investigate relationships of cumulative load and cartilage turnover biomarkers with 2-year changes in cartilage in knee osteoarthritis. From participants with Kellgren-Lawrence (KL) grades of 1 to 3, cartilage thickness and transverse relaxation time (T2) were computed from 24-month (baseline) and 48-month magnetic resonance images. Cumulative load was the interaction term of the Physical Activity Scale for the Elderly (PASE) and body mass index (BMI). Serum cartilage oligomeric matrix protein (COMP) and the nitrated form of type II collagen (Coll2-1 NO2) were collected at baseline. Multiple regressions (adjusted for baseline age, KL grade, cartilage measures, pain, comorbidity) evaluated the relationships of cumulative load and biomarkers with 2-year changes. In 406 participants (63.7 (8.7) years), interactions of biomarkers with cumulative load weakly predicted 2-year cartilage changes: (i) COMP × cumulative load explained medial tibia thickness change (R2 increased 0.062 to 0.087, p < 0.001); (ii) Coll2-1 NO2 × cumulative load explained central medial femoral T2 change (R2 increased 0.177 to 0.210, p < 0.001); and (iii) Coll2-1 NO2 × cumulative load explained lateral tibia T2 change (R2 increased 0.166 to 0.188, p < 0.001). Moderate COMP or Coll2-1 NO2 at baseline appeared protective. High COMP or Coll2-1 NO2, particularly with high BMI and low PASE, associated with worsening cartilage. Moderate serum concentrations of cartilage turnover biomarkers, at high and low physical activity, associated with maintained cartilage outcomes over 2 years. In conclusion, high concentrations of cartilage turnover biomarkers, particularly with high BMI and low physical activity, associated with knee cartilage thinning and increasing T2 over 2 years. Key Points • Higher quality cartilage may be better able to tolerate a larger cumulative load than poor quality cartilage. • Among participants enrolled in the Osteoarthritis Initiative Biomarkers Consortium Project, a representation of cumulative load exposure and its interaction with cartilage turnover biomarkers were weakly related with 2-year change in knee cartilage. • These findings suggest that cartilage turnover is a factor that modifies the relationship between loading exposure and cartilage loss in knee OA.

Cartilage Oligomeric Matrix Protein in Osteoarthritis and Obesity-Do New Considerations Emerge?

The diagnosis of osteoarthritis (OA) is based on radiological changes that are delayed, along with clinical symptoms. Early and very early diagnosis at the stage of molecular pathology may eventually offer an opportunity for early therapeutic intervention that may retard and prevent future damage. Cartilage oligomeric matrix protein (COMP) is a non-collagenous extracellular matrix protein that promotes the secretion and aggregation of collagen and contributes to the stability of the extracellular matrix. There are contradictory literature data and currently, the parameter is used only for scientific purposes and its significance is not well-determined. The serum level of COMP in patients with metabolic type OA of the knee has not been evaluated. The aim of the study was to analyze serum COMP levels in metabolic knee OA and controls with different BMI. Our results showed that the mean COMP values were significantly higher in the control group (1518.69 ± 232.76 ng/mL) compared to the knee OA patients (1294.58 ± 360.77 ng/mL) (p = 0.0012). This may be related to the smaller cartilage volume in OA patients. Additionally, COMP levels negatively correlated with disease duration (p = 0.04). The COMP level in knee OA with BMI below 30 kg/m2 (n = 61, 1304.50 ± 350.60 ng/mL) was higher compared to cases with BMI ≥ 30 kg/m2 (n = 76, 1286.63 ± 370.86 ng/mL), but the difference was not significant (p = 0.68). Whether this finding is related to specific features in the evolution of the metabolic type of knee OA remains to be determined. Interestingly, comparison of COMP levels in the controls with different BMI revealed significantly higher values in overweight and obese individuals (1618.36 ± 203.76 ng/mL in controls with BMI ≥ 25 kg/m2, n = 18, 1406.61 ± 216.41 ng/mL, n = 16; p = 0.0092). Whether this finding is associated with increased expression of COMP in the adipose tissue or with more intensive cartilage metabolism in relation to higher biomechanical overload in obese patients, considering the earlier development of metabolic type knee OA as an isolated finding, remains to be determined.

A Phase 1a Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7303509, an Anti-TGFβ3 Antibody, in Healthy Volunteers.

Transforming growth factor beta (TGFβ) cytokines (TGFβ1, TGFβ2, and TGFβ3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFβ inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFβ3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50mg, 150mg, 240mg) or subcutaneously (SC; 240mg, 675mg, 1200mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. The study enrolled 49 HVs, with a median age of 39 (range 18-73)years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (Cmax) and area under the concentration-timecurve from time 0 to infinity (AUC0-inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50mg IV) tested positive for ADAs at a single time point (day15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFβ3 inhibition. RO7303509 was well tolerated at single SC doses up to 1200mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFβ3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. ISRCTN13175485.

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.

COMP promotes pancreatic fibrosis by activating pancreatic stellate cells through CD36-ERK/AKT signaling pathways

BackgroundPancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. MethodsELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. ResultsELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-β1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. ConclusionIn conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.

Relationship between the Serum Cartilage Oligomeric Matrix Protein Concentration against Degree of Knee Osteoarthritis Pain in Elderly Patients at the Public Health Service Clinic

This study aims to assess the relationship between the serum concentration of Cartilage Oligomeric Matrix Protein (COMP) and the degree of osteoarthritis pain in elderly patients. The study was conducted at a public health service clinic, Faculty of Medicine, Syarif Hidayatullah State Islamic University (UIN) Jakarta, Indonesia. The indexes used to assess patients with OA in the knee are the Western Ontario and Mcmaster University Osteoarthritis Index (WOMAC). Sampling using the cross-sectional technique as many as 146 respondents with elderly knee OA patients. First, a physical and radiological examination is performed to confirm the diagnosis of knee OA. Second, measuring the degree of pain WOMAC. Third, the measurement of the COMP serum concentration used the ELISA test. Based on the Spearman correlation test, it was found that there was a statistically significant relationship between the COMP serum concentration and the degree of knee OA pain with the WOMAC scale in the elderly (p = 0.012). From the results of the study, it is suggested that patients maintain effective health management. Elderly patients come to community health service clinics to carry out routine/periodic checks to reduce pain. The main reason is that there is no truly effective and consistent method to prevent and cure this disease, especially for patients with age-related risk factors, excessive joint load, and a history of joint injury. AO also has an impact on a person's psychosocial well-being. These findings contribute to the study of the risk of degenerative diseases and the use of biomarkers with a level of evidence that will be more valid in the future.

Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity

BackgroundTo investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA).MethodsThis study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995–2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression.ResultsA first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17–1.80 and 1.51; 95% CI 1.18–1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99–1.74 and 1.35, 95% CI 0.99–1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10–6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD.ConclusionCOMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.

A preliminary study on the effect of loaded and unloaded exercise on N-propeptide of type II collagen and serum cartilage oligomeric matrix protein activity of articular cartilage in healthy young adults.

The serum concentration of cartilage oligomeric matrix protein (sCOMP) is considered a mechanosensitive biomarker of articular cartilage turnover, and N-propeptide of type II collagen (PIIANP), a proposed biomarker of type II collagen synthesis. Few studies have investigated the anabolic and turnover response of articular cartilage in response to acute changes in body mass during exercise. Using a repeated measure cross-over design, 15 healthy adults (age 18-30 years) performed three 30 min bouts of treadmill walking exercise under three loading conditions: (1) control (no alteration to body mass); (2) loaded (12% increase in body mass using a weighted vest); and (3) unloaded (12% decrease in body mass using lower body positive pressure). Venous blood was collected before, immediately after, and 15 and 30 min after exercise to investigate cartilage turnover (sCOMP) and anabolism (PIIANP). A main time effect (p≤0.05) revealed that sCOMP levels were significantly greater post-exercise (for all three body loading conditions) as compared to before exercise, 15 and 30 min post-exercise. There was a significant condition×time interaction (p≤0.05) for PIIANP, indicating that in the loaded condition, PIIANP concentrations at 15 min post-exercise were 13.8% greater than immediately following exercise, and 12.9% greater than before exercise. In summary, sCOMP concentration was acutely increased with all three loading conditions. However, PIIANP increased only after exercise in the loaded condition, suggesting an acute anabolic effect on articular cartilage. NCT05925244.

Comparative Study of the Pain, Function, and Biomarkers of Joint Disease in the Transition to Adulthood in Individuals With and Without Cerebral Palsy.

Biomarkers have potential to identify early signs of joint disease. This study compared joint pain and function in adolescents and young adults with cerebral palsy compared with individuals without. This cross-sectional study compared individuals with cerebral palsy ( n = 20), aged 13-30 yrs with Gross Motor Function Classification System I-III and age-matched individuals without cerebral palsy ( n = 20). Knee and hip joint pain measured using Numeric Pain Rating Scale and Knee injury and Osteoarthritis Outcome Score and Hip dysfunction and Osteoarthritis Outcome Score surveys. Objective strength and function were also measured. Biomarkers for tissue turnover (serum cartilage oligomeric matrix protein, urinary C-terminal crosslinked telopeptide of type II collagen) and cartilage degradation (serum matrix metalloproteinase 1, matrix metalloproteinase 3) were measured in blood and urinary samples. Individuals with cerebral palsy had increased knee and hip joint pain, reduced leg strength, reduced walking and standing speeds, and ability to carry out activities of daily living ( P < 0.005) compared with controls. They also had higher serum matrix metalloproteinase 1 ( P < 0.001) and urinary C-terminal crosslinked telopeptide of type II collagen levels ( P < 0.05). Individuals with cerebral palsy who were Gross Motor Function Classification System I and II demonstrated reduced hip joint pain ( P = 0.02) and higher matrix metalloproteinase 1 levels ( P = 0.02) compared with Gross Motor Function Classification System III. Individuals with cerebral palsy with less severe mobility deficits had higher matrix metalloproteinase 1 levels likely due to more prolonged exposure to abnormal joint loading forces but experienced less joint pain.

Delayed cartilage oligomeric matrix protein response to loading is associated with femoral cartilage composition post-ACLR.

To determine associations between immediate and delayed response of serum cartilage oligomeric matrix protein (sCOMP) to loading (i.e., 3000 walking steps) and femoral cartilage interlimb T1ρ relaxation times in individual's post-anterior cruciate ligament reconstruction (ACLR). This cross-sectional study included 20 individuals 6-12months following primary ACLR (65% female, 20.5 ± 4.0years old, 24.9 ± 3.0kg/m2, 7.3 ± 1.5months post-ACLR). Serum samples were collected prior to, immediately following, and 3.5h following walking 3000 steps on a treadmill at habitual walking speed. sCOMP concentrations were processed using enzyme-linked immunosorbent assays. Immediate and delayed absolute sCOMP responses to loading were evaluated immediately and 3.5h post-walking, respectively. Participants underwent bilateral magnetic resonance imaging with T1ρ sequences to calculate resting femoral cartilage interlimb T1ρ relaxation time ratios between limbs (i.e., ACLR/Uninjured limb). Linear regression models were fitted to determine associations between sCOMP response to loading and femoral cartilage T1ρ outcomes controlling for pre-loading sCOMP concentrations. Greater increases in delayed sCOMP response to loading were associated with greater lateral (∆R2 = 0.29, p = 0.02) but not medial (∆R2 < 0.01, p = 0.99) femoral cartilage interlimb T1ρ ratios. Associations between immediate sCOMP response to loading with femoral cartilage interlimb T1ρ ratios were weak and non-significant (∆R2 range = 0.02-0.09, p range = 0.21-0.58). Greater delayed sCOMP response to loading, a biomarker of cartilage breakdown, is associated with worse lateral femoral cartilage composition in the ACLR limb compared to the uninjured limb. Delayed sCOMP response to loading may be a more indicative metabolic indicator linked to deleterious changes in composition than immediate sCOMP response.

Immediate Effects of Walking With a Knee Brace After Anterior Cruciate Ligament Reconstruction: A Biomechanical, Biochemical, and Structural Approach.

Individuals who undergo anterior cruciate ligament reconstruction (ACLR) are at higher risk of posttraumatic osteoarthritis. Altered joint tissue loading caused by aberrant gait biomechanics leads to deleterious changes in joint health linked to the onset of posttraumatic osteoarthritis. Knee braces have been used to modify joint tissue loading in individuals with joint injury, yet the effects of walking with a brace after ACLR on biomechanical, biochemical, and structural cartilage outcomes are unknown. To compare biomechanical, biochemical, and structural outcomes between braced and nonbraced walking in individuals with ACLR. Crossover study. Research laboratory. A total of 34 individuals with unilateral ACLR (18 females, 16 males; time since ACLR = 50.1 ± 36.8 months). Gait biomechanics were assessed during braced and unbraced conditions on separate days. Vertical ground reaction force, knee-flexion angle, and internal knee-extension moment waveforms were evaluated throughout the stance phase and compared between conditions. Percentage changes in serum cartilage oligomeric matrix protein (%ΔCOMP) and femoral cartilage cross-sectional area (%ΔCSA) measured via ultrasound were calculated after a 3000-step walking protocol. Braced walking increased the knee-flexion angle (largest difference = 3.56°; Cohen d effect size = 1.72) and knee-extension moment (largest difference = -0.48% body weight × height; Cohen d effect size = -1.14) compared with nonbraced walking but did not influence vertical ground reaction force. Whereas no difference (P = .20) in %ΔCOMP existed between the braced and nonbraced conditions in the entire cohort (n = 30 with complete blood data), a larger increase (P = .04) in %ΔCOMP was seen during nonbraced than braced walking in individuals who demonstrated increased COMP during nonbraced walking. No difference (P = .86) in %ΔCSA was present between the braced and nonbraced conditions. Braced walking may improve sagittal-plane gait biomechanics and %ΔCOMP in a subset of individuals who demonstrate a typical increased COMP response to load (ie, increase in COMP) after nonbraced walking.

The effects of a 6-month weight loss intervention on physical function and serum biomarkers in older adults with and without osteoarthritis

ObjectiveTo examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA). Design59 individuals ≥60 years old with obesity and a functional impairment were enrolled into this IRB approved clinical trial and randomized into one of two 6-month weight loss arms: a higher protein hypocaloric diet or a standard protein hypocaloric diet. All participants were prescribed individualized 500-kcal daily-deficit diets, with a goal of 10% weight loss. Additionally, participants participated in three, low-intensity, exercise sessions per week. Physical function, serum biomarkers and body composition data were assessed at the baseline and 6-month timepoints. Statistical analyses assessed the relationships between biomarkers, physical function, body composition, and OA status as a result of the intervention. ResultsNo group effects of dietary intervention were detected on any outcome measures (multiple p ​> ​0.05). During the 6-month trial, participants lost 6.2 ​± ​4.0% of their bodyweight (p ​< ​0.0001) and experienced improved physical function on the Short-Performance-Physical-Battery (p ​< ​0.0001), 8-foot-up-and-go (p ​< ​0.0001), and time to complete 10-chair-stands (p ​< ​0.0001). Adiponectin concentrations (p ​= ​0.0480) were elevated, and cartilage oligomeric matrix protein (COMP) concentrations (p ​< ​0.0001) were reduced; further analysis revealed that reductions in serum COMP concentrations were greater in OA-negative individuals. ConclusionsThese results suggest that weight loss in older adults with and without OA may provide a protective effect to cartilage and OA. In particular, OA-negative individuals may be able to mitigate changes associated with OA through weight loss.

A STUDY OF CARTILAGE OLIGOMERIC MATRIX PROTEIN (COMP) &amp; TUMOR NECROSIS FACTOR - IN POST MENOPAUSAL KNEE OSTEOARTHRITIC FEMALE PATIENT.

Osteoarthritis is a type of arthritis that occurs when the flexible ends of tissues at the end of the bones wear down and it could be due to various causes affecting the daily life of the people. Women are the most important part of society and according to studies it was stated women are more affected than men. There are many biochemical markers involved in the diagnosis of osteoarthritis with other investigations like radiological, and clinical approaches. Here in this study the Cartilage oligomeric matrix protein (COMP) and Tumor necrosis factor – alpha (TNF-?) were determined in post-menopausal knee osteoarthritic female patients and normal healthy subjects taking into consideration of all the exclusion and inclusion criteria. The samples were collected and tests were performed by ELISA. The study suggested that raised levels of the serum COMP &amp; TNF-? in the study group were age-related changes with inflammation and infection at the knee joint which were suggestive of knee osteoarthritis.

The Increase Of Load-Induced Serum Cartilage Oligomeric Matrix Protein Concentration Correlates With T2 Relaxation Time In Participants With Anterior Cruciate Ligament Injury

The Increase Of Load-Induced Serum Cartilage Oligomeric Matrix Protein Concentration Correlates With T2 Relaxation Time In Participants With Anterior Cruciate Ligament Injury

Acute And Delayed Effects Of Modifying Load During Walking On Serum Cartilage Oligomeric Matrix Protein Following Acl Reconstruction

Acute And Delayed Effects Of Modifying Load During Walking On Serum Cartilage Oligomeric Matrix Protein Following Acl Reconstruction