RESUMO
AIMS: This 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 METHODS: In 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-1ß) 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. RESULTS: Following a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1ß 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). CONCLUSION: Metformin 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-1ß levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores. GOV ID: NCT05638893/Registered December 6, 2022 - Retrospectively.
Assuntos
Metformina , Obesidade , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Método Duplo-Cego , Metformina/administração & dosagem , Metformina/farmacologia , Masculino , Pessoa de Meia-Idade , Feminino , Obesidade/tratamento farmacológico , Idoso , Celecoxib/administração & dosagem , Celecoxib/farmacologia , Interleucina-1beta/sangue , Proteína de Matriz Oligomérica de Cartilagem/sangue , Resultado do Tratamento , Quimioterapia Combinada , Colágeno Tipo I/sangueRESUMO
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.
Assuntos
Proteína de Matriz Oligomérica de Cartilagem , Obesidade , Osteoartrite do Joelho , Humanos , Proteína de Matriz Oligomérica de Cartilagem/sangue , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Obesidade/metabolismo , Obesidade/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Idoso , Índice de Massa Corporal , Biomarcadores/sangue , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Estudos de Casos e ControlesRESUMO
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.
Assuntos
Biomarcadores , Proteína de Matriz Oligomérica de Cartilagem , Cartilagem Articular , Colágeno Tipo II , Articulação do Joelho , Imageamento por Ressonância Magnética , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/metabolismo , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Pessoa de Meia-Idade , Feminino , Biomarcadores/sangue , Masculino , Proteína de Matriz Oligomérica de Cartilagem/sangue , Idoso , Articulação do Joelho/diagnóstico por imagem , Colágeno Tipo II/sangue , Progressão da Doença , Suporte de Carga , Índice de Massa CorporalRESUMO
OBJECTIVE: The object of this study was to determine the effect of EAS (Equine-Assisted Services) on arthritis conditions, as measured by the sTnT (Skeletal troponin) and COMP (cartilage oligomeric matrix proteins) biomarkers, compared to an exercise attention control intervention. DESIGN: This was a secondary analysis of a randomized clinical trial comparing equine-assisted therapy to exercise education attention-control on cartilage and skeletal biomarkers in adults with arthritis. Twenty-one adults (Mage = 64 years) with arthritis who attended rheumatology clinics in the midwestern United States participated. RESULTS: No changes were found in sTnT from baseline to week six within either intervention nor were there differences in changes between the two groups (p = 0.91). COMP increased from baseline to week six for both conditions, suggesting increased deterioration of cartilage and joints. Although the attention-control condition demonstrated larger increases in cartilage oligomeric matrix proteins level, compared to the EAS condition, these differences were not statistically (p = 0.58) or clinically significant (i.e., trivial effect, d = -0.16). When 3 outliers were removed, the differences in changes between EAT and attention-control group could be arguably of clinical significance (d = - 0.33), suggesting that the attention-control group demonstrated larger increases in levels of COMP than those in the EAS condition, though this difference was not statistically significant (p = 0.28). CONCLUSION: Although equine-assisted therapy may reduce pain and improve quality of life for adults with arthritis, findings here are not fully corroborated with biomarkers.
Assuntos
Biomarcadores , Proteína de Matriz Oligomérica de Cartilagem , Terapia Assistida por Cavalos , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Biomarcadores/sangue , Feminino , Masculino , Idoso , Proteína de Matriz Oligomérica de Cartilagem/sangue , Terapia Assistida por Cavalos/métodos , Cavalos , Artrite/terapia , Animais , Cartilagem/metabolismoRESUMO
Owing to chondral or meniscal pathology sustained at the time of injury, patients who sustain anterior cruciate ligament injury are at risk of knee osteoarthritis (OA). Thus, recognition of early OA is critical. Detection of joint space narrowing on radiography has been described as outdated, and furthermore, the different descriptions of the Kellgren-Lawrence criteria have an impact on the classification of OA of the lowest grade (Kellgren-Lawrence grade ≥ 1). Serum cartilage oligomeric matrix protein (COMP) may allow detection of early OA in patients with anterior cruciate ligament deficiency because significantly higher levels have been observed in patients with early OA than in patients with non-early OA. Serum COMP appears to be the most useful of the biomarkers studied. Prior studies have shown correlations with OA in animal models and via magnetic resonance imaging evaluation. However, I would be hesitant about widespread use. It is possible that the serum COMP level reflects not only cartilage damage but also synovitis. This may be particularly misleading in patients with diagnoses of rheumatologic disorders and/or undiagnosed genetic HLA-B27 variants.
Assuntos
Lesões do Ligamento Cruzado Anterior , Osteoartrite do Joelho , Sinovite , Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Biomarcadores/sangue , Proteína de Matriz Oligomérica de Cartilagem/sangue , Humanos , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico por imagem , Sinovite/diagnóstico por imagemRESUMO
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The incidence of early OA arthroscopic cartilage findings was â¼30% 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. LEVEL OF EVIDENCE: â ¢, retrospective comparative study.
Assuntos
Lesões do Ligamento Cruzado Anterior , Proteína de Matriz Oligomérica de Cartilagem , Osteoartrite do Joelho , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/diagnóstico , Lesões do Ligamento Cruzado Anterior/cirurgia , Biomarcadores , Proteína de Matriz Oligomérica de Cartilagem/sangue , Criança , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR. DESIGN: Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score. RESULTS: One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97-5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41-23.81]) T1ρ relaxation times. CONCLUSION: Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.
Assuntos
Reconstrução do Ligamento Cruzado Anterior , Proteína de Matriz Oligomérica de Cartilagem/sangue , Cartilagem Articular/diagnóstico por imagem , Quimiocina CCL2/sangue , Articulação do Joelho/diagnóstico por imagem , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.
Assuntos
Proteína C-Reativa/metabolismo , Proteína de Matriz Oligomérica de Cartilagem/sangue , Colágeno Tipo III/sangue , Osteoartrite do Joelho/sangue , Dor/sangue , Sinovite/sangue , Idoso , Biomarcadores/sangue , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Dor/diagnóstico por imagem , Dor/patologia , Índice de Gravidade de Doença , Sinovite/diagnóstico por imagem , Sinovite/patologiaRESUMO
BACKGROUND: Diagnosis of intervertebral disc degeneration (IVDD) is challenging at the early stage. The cartilage oligomeric matrix protein (COMP) and extracellular matrix degradation products of C-telopeptide of type II collagen (CTX-II) serve as markers for the serological diagnosis of IVDD. Oxidative stress might cause IVDD and matrix degeneration. METHODS: A total of 128 male adult Sprague-Dawley (SD) rats were randomly and equally assigned to the experimental and control groups. The experimental group was used to construct IVDD models by acupuncture, while the control group underwent sham operation. The animals were executed every week for 8 weeks after intervertebral disc acupuncture, and serum samples were collected for the estimation of CTX-II and COMP concentrations by enzyme-linked immunosorbent assay (ELISA). Also, the histological changes and caudal magnetic resonance imaging (MRI) changes were examined in the intervertebral disc. RESULTS: IVDD in rats worsened with prolonged follow-up after acupuncture. At all the time points, the experimental group showed altered histological and caudal vertebra MRI signals, and serum CTX-II and COMP concentrations were significantly greater than those of the control group. These levels increase with the process of IVDD. CONCLUSION: Serum CTX-II and COMP estimation is a reliable method to diagnose IVDD, and their concentrations show a positive correlation with the process of IVDD.
Assuntos
Colágeno Tipo II/sangue , Degeneração do Disco Intervertebral/diagnóstico por imagem , Fragmentos de Peptídeos/sangue , Regulação para Cima , Animais , Biomarcadores/sangue , Proteína de Matriz Oligomérica de Cartilagem/sangue , Modelos Animais de Doenças , Diagnóstico Precoce , Degeneração do Disco Intervertebral/metabolismo , Imageamento por Ressonância Magnética , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.
Assuntos
Atresia Biliar/patologia , Proteína de Matriz Oligomérica de Cartilagem/análise , Cirrose Hepática/patologia , Adolescente , Atresia Biliar/sangue , Atresia Biliar/complicações , Atresia Biliar/genética , Biomarcadores/análise , Proteína de Matriz Oligomérica de Cartilagem/sangue , Proteína de Matriz Oligomérica de Cartilagem/genética , Criança , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/genética , Masculino , RNA Mensageiro/genéticaRESUMO
PURPOSE: To investigate the association between age, physical activity, femoral trochlear cartilage thickness and biomarkers of tissue metabolism in a cross-sectional sample of adult males. This study utilizes several emerging biomarkers that have been associated with early joint degenerative changes; serum COMP (cartilage oligomeric matrix protein), HA (hyaluronan) and lubricin. METHODS: Eighty-one males (age: mean (range): 43(18-70) years; body mass index: 25.2 (21.0-30.6) kg/m2) volunteered. Resting serum COMP, HA and lubricin concentrations were determined via commercially available enzyme-linked immunosorbent assay (ELISA) and femoral trochlear cartilage thickness via supra-patellar ultrasound imaging. Physical activity levels were assessed using questionnaires. Statistical analyses were performed using correlation and regression analyses. RESULTS: Age was correlated with lateral trochlear cartilage thickness (r = - 0.372; p < 0.01) and serum COMP (r = 0.342; p < 0.01). 7-day physical activity was correlated with serum COMP (r = 0.357, p < 0.01), and 12-month physical activity with both lateral trochlear cartilage thickness (r = 0.340, p = 0.01) and serum HA (r = 0.296, p < 0.05). Regression analyses revealed that age significantly accounted for the variability in lateral cartilage thickness and serum COMP, following the adjustment for potential cofounders. However, the association between age and lateral trochlear cartilage thickness was not moderated by physical activity levels (all p > 0.05). CONCLUSION: This study indicates that older age may be associated with thinner lateral trochlear cartilage and higher cartilage turnover. Being physically active may also be positive for lateral trochlear cartilage thickness. However, overall, both age and physical activity level only account for a small amount of the variability in cartilage thickness and serum biomarkers.
Assuntos
Biomarcadores/sangue , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/metabolismo , Exercício Físico/fisiologia , Adolescente , Adulto , Fatores Etários , Animais , Proteína de Matriz Oligomérica de Cartilagem/sangue , Fêmur , Glicoproteínas/sangue , Humanos , Ácido Hialurônico/sangue , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
OBJECTIVE: To address the need for early knee osteoarthritis (OA) markers by testing if longitudinal cartilage thickness changes are associated with specific biomechanical and biological measures acquired at a baseline test in asymptomatic aging subjects. DESIGN: Thirty-eight asymptomatic subjects over age 45 years were studied at baseline and at an average of 7-9 year follow-up. Gait mechanics and knee MRI were measured at baseline and MRI was obtained at follow-up to assess cartilage thickness changes. A subset of the subjects (n = 12) also had serum cartilage oligomeric matrix protein measured at baseline in response to a mechanical stimulus (30-min walk) (mCOMP). Baseline measures, including the knee extension (KEM), flexion (KFM), adduction (KAM) moments and mCOMP, were tested for associations with cartilage thickness changes in specific regions of the knee. RESULTS: Cartilage change in the full medial femoral condyle (p = 0.005) and external medial femoral region (p = 0.041) was negatively associated with larger early stance peak KEM. Similarly, cartilage change in the full medial femoral region (p = 0.009) and medial femoral external region (p = 0.043) was negatively associated with larger first peak KAM, while cartilage change in the anterior medial tibia was positively associated with larger first peak KAM (p = 0.003). Cartilage change in the anterior medial tibia was also significantly associated (p = 0.011) with mCOMP levels 5.5-h post-activity (percentage of pre-activity levels). CONCLUSIONS: Interactions found between gait, mechanically-stimulated serum biomarkers, and cartilage thickness in an at-risk aging asymptomatic population suggest the opportunity for early detection of OA with new approaches that bridge across disciplines and scales.
Assuntos
Proteína de Matriz Oligomérica de Cartilagem/sangue , Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Envelhecimento/fisiologia , Doenças Assintomáticas , Biomarcadores/sangue , Fenômenos Biomecânicos/fisiologia , Cartilagem Articular/fisiopatologia , Diagnóstico Precoce , Feminino , Seguimentos , Análise da Marcha , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/fisiopatologiaRESUMO
OBJECTIVE: COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis. Approach and Results: Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metalloproteinase-1), TRAIL-R2 (tumor necrosis factor-related apoptosis-inducing ligand receptor 2), ITGB1BP2 (integrin beta 1 binding protein 2), and COMPneo were predictive of stenosis. Conversely, KLK6 (kallikrein-6), COMPtotal, NEMO (nuclear factor-kappa-B essential modulator), SRC (Proto-oncogene tyrosine-protein kinase Src), SIRT2 (SIR2-like protein), CD40 (cluster of differentiation 40), TF (tissue factor), MP (myoglobin), and RAGE (receptor for advanced glycation end-products) were predictive of the control group. Model reproducibility was good with the receiver operating characteristic plot area under the curve being 0.86. When comparing the plaque group and stenosis group, COMPneo, GAL (galanin), and PTX3 (pentraxin-related protein PTX3) were predictive of stenosis. Model reproducibility was excellent (receiver operating characteristic plot area under the curve 0.92). COMPneo was detected in smooth muscle-, endothelial-, and foam-cells in carotid stenosis. CONCLUSIONS: Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract: A graphic abstract is available for this article.
Assuntos
Estenose das Carótidas/sangue , Proteína de Matriz Oligomérica de Cartilagem/sangue , Proteína de Matriz Oligomérica de Cartilagem/imunologia , Epitopos/sangue , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estenose das Carótidas/imunologia , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Epitopos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Placa Aterosclerótica/sangue , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/metabolismo , Proto-Oncogene Mas , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/imunologiaRESUMO
This study aimed to determine if changes in knee adduction moment (KAM) after 6 months of variable-stiffness shoe wear are associated with changes in symptoms or serum levels of cartilage oligomeric matrix protein (COMP) following a mechanical stimulus in subjects with medial knee osteoarthritis (OA). Twenty-five subjects were enrolled in the study and assigned a variable-stiffness shoe, and 19 subjects completed the 6-month follow-up. At baseline and follow-up subjects underwent gait analysis in control and variable-stiffness shoes, completed Western Ontario and McMaster Universities (WOMAC) questionnaires, and serum COMP concentrations were measured immediately before, 3.5 and 5.5 hours after a 30-minute walking activity. Relationships between changes in KAM (first peak and impulse) and changes in (a) COMP levels in response to the 30-minute walking activity and (b) WOMAC scores from baseline to 6-month follow-up were assessed by Pearson correlation coefficients. Changes in first peak KAM were associated with changes in COMP levels 5.5 hours postactivity from baseline to follow-up (R = .564, P = .045). Subjects with greater reductions in KAM had larger decreases in COMP (expressed as a percent of preactivity levels) at follow-up. Subjects with greater reductions in KAM impulse had significantly greater improvements in WOMAC Pain (R = -.56, P = .015) and Function (R = -.52, P = .028) scores at follow-up. The study results demonstrated the magnitude of reduction in the KAM wearing a variable-stiffness shoe is associated with decreases in mechanically stimulated COMP levels and pain/function. This work suggests that interactions between COMP and joint loading during walking should be further investigated in future studies of treatment outcomes in OA.
Assuntos
Proteína de Matriz Oligomérica de Cartilagem/sangue , Articulação do Joelho/fisiologia , Osteoartrite do Joelho/terapia , Sapatos/estatística & dados numéricos , Idoso , Feminino , Órtoses do Pé/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/complicações , Dor/etiologia , Dor/prevenção & controle , Estudos Prospectivos , Índice de Gravidade de Doença , Suporte de CargaRESUMO
Osteoarthritis (OA) is the most common chronic degenerative joint disease which causes substantial joint pain, deformity and loss of activities of daily living. Currently, there are over 500 million OA cases worldwide, and there is an urgent need to identify biomarkers for early detection, and monitoring disease progression in patients without obvious radiographic damage to the joint. We have used regression modelling to describe the association of 19 of the currently available biomarkers (predictors) with key radiographic and clinical features of OA (outcomes) in one of the largest and best characterised OA cohort (NIH Osteoarthritis Initiative). We demonstrate that of the 19 currently available biomarkers only 4 (serum Coll2-1 NO2, CS846, COMP and urinary CTXII) were consistently associated with established radiographic and/or clinical features of OA. These biomarkers are independent of one another and provide additional predictive power over, and above established predictors of OA such as age, gender, BMI and race. We also show that that urinary CTXII had the strongest and consistent associations with clinical symptoms of OA as well as radiographic evidence of joint damage. Accordingly, urinary CTXII may aid in early diagnosis of OA in symptomatic patients without radiographic evidence of OA.
Assuntos
Proteína de Matriz Oligomérica de Cartilagem/sangue , Sulfatos de Condroitina/sangue , Colágeno Tipo II/sangue , Colágeno Tipo II/urina , Osteoartrite do Joelho/diagnóstico , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/urina , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
Biomarkers of cartilage metabolism are sensitive to changes in the biological and mechanical environment and can indicate early changes in cartilage homeostasis. The purpose of this study was to determine if a daily locomotion replacement program can serve as a countermeasure for changes in cartilage biomarker serum concentration caused by immobilization. Ten healthy male subjects (mean ± 1 standard deviation; age: 29.4 ± 5.9 years; body mass: 77.7 ± 4.1 kg) participated in the crossover 5-day bed rest study with three interventions: control (CON), standing (STA), and locomotion replacement training (LRT). Serum samples were taken before, during, and after bed rest. Biomarker concentrations were measured using commercial enzyme-linked immunosorbent assays. Cartilage oligomeric matrix protein (COMP) levels after 24 hours of bed rest decreased independently of the intervention (-16.8% to -9.8%) and continued to decrease until 72 hours of bed rest (minimum, -23.2% to -20.6%). LRT and STA did not affect COMP during bed rests (P = .056) but there was a strong tendency for a slower decrease with LRT (-9.4%) and STA (-11.7%) compared with CON (-16.8%). MMP-3 levels decreased within the first 24 hours of bed rest (CON: -22.3%; STA: -14.7%; LRT: -17%) without intervention effect. Both COMP and MMP-3 levels recovered to baseline levels during the 6-day recovery period. MMP-1, MMP-9, and TNF-α levels were not affected by immobilization or intervention. COMP and MMP-3 are mechano-sensitive cartilage biomarkers affected by immobilization, and simple interventions such as standing upright or LRT during bed rest cannot prevent these changes. Clinical significance: simple locomotion interventions cannot prevent cartilage biomarker change during bed rest.
Assuntos
Repouso em Cama/efeitos adversos , Proteína de Matriz Oligomérica de Cartilagem/sangue , Cartilagem/metabolismo , Terapia por Exercício/métodos , Metaloproteinases da Matriz Secretadas/sangue , Adulto , Decúbito Inclinado com Rebaixamento da Cabeça/efeitos adversos , Humanos , Locomoção , Masculino , Voo Espacial , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
This study assessed the influence of a 10-day hypoxic bed rest on cartilage biomarkers and subchondral bone density across the patellofemoral joint (PFJ). Within clinical settings hypoxic tissue may arise in several types of disorders. Furthermore, a hypoxic environment is being considered for space flight habitats in the near future. Female participants (N = 12) participated in this study comprising three 10-day interventions: hypoxic ambulation (HAMB), normoxic bed rest (NBR), and hypoxic bed rest (HBR). Venous samples were collected prior to (day -2: Pre) and during the intervention (days 2 and 5), immediately before reambulation (D11) and 24 hr post intervention (R1). Blood samples were analyzed for: aggrecan, hyaluronan, Type IIA procollagen amino terminal propeptide (PIIANP), and cartilage oligomeric matrix protein (COMP). Total bone mineral density (BMD) in eight regions (2 mm × 10 mm) across the PFJ was determined. The three interventions (HAMB, HBR, and NBR) did not induce any significant changes in the cartilage biomarkers of hyaluronan or PIIANP. Aggrecan increased during the HAMB trial to 2.02 fold the Pre value. COMP decreased significantly in both NBR & HBR compared to HAMB on D5. There were significant differences in BMD measured across the PFJ from cortical patellar bone (735 to 800 mg/cm3 ) to femur trabecular (195 to 226 mg/cm3 ). However, there were no significant changes in BMD from Pre to Post bed rest. These results indicate that there were no significant detectable effects of inactivity/unloading on subchondral bone density. The biomarker of cartilage, COMP, decreased on D5, whereas the addition of hypoxia to bed rest had no effect, it appears that hypoxia in combination with ambulation counteracted this decrease.
Assuntos
Repouso em Cama , Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Cartilagem/metabolismo , Hipóxia/metabolismo , Agrecanas/sangue , Biomarcadores/sangue , Osso e Ossos/patologia , Cartilagem/patologia , Proteína de Matriz Oligomérica de Cartilagem/sangue , Feminino , Humanos , Ácido Hialurônico/sangue , Hipóxia/sangue , Hipóxia/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Estudos ProspectivosRESUMO
The complete laboratory and clinical instrumental examination was conducted, it included serum COMP test, circadian excretion of type II collagen C-terminal telopeptides Urine CartiLaps (СТХ II) and Т2 relaxometry in 29 patients of both sexes of the main group with early (0-I) X-ray osteoarthrosis stages, 30 subjects of comparison group with no X-ray osteoarthrosis evidences aged 44.7±5.9 years and 25 healthy subjects aged 26.3±2.6 years of the control group. The increase (Ñ<0,05) of COMP and Urine CartiLaps levels as well as the increase of Т2 relaxation signal was found at early osteoarthrosis evidences. It was proven that there was (Ñ<0.01) a connection (R=0.8) between COMP and Urine CTX II levels as well as (Ñ<0.05) results of Т2 relaxometry (R=0.8). It was proven that collagen anisotropy and formation of chondromalacia areas as Т2 relaxometry showed in patients with early OA evidences were connected with accumulation of serum COMP and increase of type II collagen circadian renal excretion. The combination of laboratory and radiological methods of articular hyaline cartilage assessment may be used for finding early osteoarthrosis stages.
Assuntos
Doenças Metabólicas/diagnóstico , Osteoartrite/diagnóstico , Adulto , Proteína de Matriz Oligomérica de Cartilagem/sangue , Estudos de Casos e Controles , Colágeno Tipo II/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/urina , Adulto JovemRESUMO
OBJECTIVES: 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). METHOD: 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. RESULTS: In this OA cohort, after adjustment for age, sex, and BMI, the presence of pathological effusion-synovitis was associated with serum levels of COMP (ß: 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. CONCLUSIONS: 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.
Assuntos
Proteína C-Reativa/metabolismo , Proteína de Matriz Oligomérica de Cartilagem/sangue , Cartilagem Articular/patologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/patologia , Sinovite/patologia , Idoso , Medula Óssea/patologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteoartrite do Joelho/sangue , Osteófito/patologia , Medição da Dor , Radiografia , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
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.