RESUMEN
BACKGROUND: Osteoarthritis (OA) is a degenerative osteoarticular disease, involving genetic predisposition. How the risk variants confer the risk of OA through their effects on proteins remains largely unknown. Therefore, we aimed to discover new and effective drug targets for OA and its subtypes. METHODS: A proteome-wide association study (PWAS) was performed based on OA and its subtypes genome-wide association studies (GWAS) summary datasets and the protein quantitative trait loci (pQTL) data. Subsequently, Mendelian randomization (MR) and colocalization analysis was conducted to estimate the associations between protein and OA risk. The replication analysis was performed in an independent dataset of human plasma pQTL data. RESULTS: The abundance of seven proteins was causally related to OA, two proteins to knee OA and six proteins to hip OA, respectively. We replicated 2 of these proteins using an independent pQTL dataset. With the further support of colocalization, and higher ECM1 level was causally associated with a higher risk of OA and hip OA. Higher PCSK1 level was causally associated with a lower risk of OA. And higher levels of ITIH1, EFEMP1, and ERLEC1 were associated with decreased risk of hip OA. CONCLUSION: Our study provides new insights into the genetic component of protein abundance in OA and a promising therapeutic target for future drug development.
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Estudio de Asociación del Genoma Completo , Proteoma , Sitios de Carácter Cuantitativo , Humanos , Osteoartritis/genética , Osteoartritis/sangre , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/sangre , Predisposición Genética a la Enfermedad/genética , Osteoartritis de la Cadera/genética , Osteoartritis de la Cadera/sangre , Análisis de la Aleatorización Mendeliana , Masculino , Femenino , Terapia Molecular Dirigida/métodosRESUMEN
BACKGROUND/OBJECTIVES: The objective of this study was to test the hypothesis that vitamin D deficiency (i.e., serum 25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/mL) associates with the increased occurrence and shortened time to a knee osteoarthritis (OA) diagnosis after anterior cruciate ligament reconstruction (ACLR). METHODS: This study consisted of a retrospective, case-control design. The inclusion criteria consisted of (1) patients (≥18 y) who underwent arthroscopic ACLR with (cases; n = 28) and without (controls; n = 56) a subsequent knee OA diagnosis (≥90 d from the date of ACLR) and (2) with a documented serum 25(OH)D concentration after ACLR (and before a knee OA diagnosis for the cases). Controls were matched (2:1) to cases based on sex, age at ACLR, date of ACLR, and body mass index. After matching, patients were separated into two groups: (1) vitamin D deficient (serum 25(OH)D ≤ 20 ng/mL) or (2) non-vitamin D deficient (serum 25(OH)D > 20 ng/mL). Data were extracted from the medical records. RESULTS: Thirty-one percent (n = 26) of patients included were vitamin D deficient. Fifty percent (n = 13) of the vitamin D deficient and twenty-six percent (n = 15) of the non-vitamin D deficient patients were subsequently diagnosed with knee OA (p = 0.03). Time from ACLR to a knee OA diagnosis was significantly (p = 0.02) decreased in the vitamin D deficient (OA-free interval, 95% confidence interval [CI] = 7.9 to 10.9 y) compared to the non-vitamin D deficient group (OA-free interval, 95% CI = 10.5 to 12.5 y). CONCLUSIONS: Vitamin D deficiency after ACLR may serve as a prognostic biomarker for knee OA following ACLR.
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Reconstrucción del Ligamento Cruzado Anterior , Osteoartritis de la Rodilla , Deficiencia de Vitamina D , Vitamina D , Humanos , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Estudios Retrospectivos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangre , Masculino , Femenino , Adulto , Vitamina D/sangre , Vitamina D/análogos & derivados , Estudios de Casos y Controles , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To establish an optimal preoperative HbA1c threshold that enhances surgical outcomes and minimises postoperative complications in diabetic patients undergoing elective total knee arthroplasty (TKA). STUDY DESIGN: Prospective cohort study. Place and Duration of the Study: Department of Orthopaedics, First People's Hospital of Lianyungang, China, from January 2021 to March 2024. METHODOLOGY: A total of 152 diabetic patients scheduled for elective TKA were included. Data on preoperative HbA1c levels were collected and analysed to assess their impact on postoperative outcomes using the Oxford Knee Score (OKS). Patients were divided into groups based on HbA1c levels and compared for functional and pain recovery one year postoperatively. Statistical analyses included binary and multivariate logistic regression, with an emphasis on the minimum clinically important difference for OKS. RESULTS: Patients with a preoperative HbA1c below 7.35mmol/L exhibited significantly better functional and pain recovery outcomes at one-year post-TKA. The receiver operating characteristic curve (ROC) analysis confirmed the predictive power of HbA1c, with an Area Under the Curve of 0.734 for functional improvement and 0.721 for pain improvement. CONCLUSION: The study identifies 7.35mmol/L as the optimal preoperative HbA1c threshold for diabetic patients undergoing elective TKA, with lower levels associated with improved functional and pain outcomes. Maintaining HbA1c below this level preoperatively can significantly enhance postoperative recovery and patient satisfaction. KEY WORDS: Diabetes mellitus, Total knee arthroplasty, Haemoglobin A1c, Oxford knee score.
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Artroplastia de Reemplazo de Rodilla , Procedimientos Quirúrgicos Electivos , Hemoglobina Glucada , Humanos , Hemoglobina Glucada/análisis , Femenino , Masculino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Diabetes Mellitus/sangre , Recuperación de la Función , Complicaciones Posoperatorias/sangre , Resultado del Tratamiento , China , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangreRESUMEN
BACKGROUND: Anterior cruciate ligament injury and anterior cruciate ligament reconstruction (ACLR) are risk factors for symptomatic posttraumatic osteoarthritis (PTOA). After ACLR, individuals demonstrate altered joint tissue metabolism indicative of increased inflammation and cartilage breakdown. Serum biomarker changes have been associated with tibiofemoral cartilage composition indicative of worse knee joint health but not with PTOA-related symptoms. PURPOSE/HYPOTHESIS: The purpose of this study was to determine associations between changes in serum biomarker profiles from the preoperative sample collection to 6 months after ACLR and clinically relevant knee PTOA symptoms at 12 months after ACLR. It was hypothesized that increases in biomarkers of inflammation, cartilage metabolism, and cartilage degradation would be associated with clinically relevant PTOA symptoms after ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Individuals undergoing primary ACLR were included (N = 30). Serum samples collected preoperatively and 6 months after ACLR were processed to measure markers indicative of changes in inflammation (ie, monocyte chemoattract protein 1 [MCP-1]) and cartilage breakdown (ie, cartilage oligomeric matrix protein [COMP], matrix metalloproteinase 3, ratio of type II collagen breakdown to type II collagen synthesis). Knee injury and Osteoarthritis Outcome Score surveys were completed at 12 months after ACLR and used to identify participants with and without clinically relevant PTOA-related symptoms. K-means cluster analyses were used to determine serum biomarker profiles. One-way analyses of variance and logistic regressions were used to assess differences in Knee injury and Osteoarthritis Outcome Score subscale scores and clinically relevant PTOA-related symptoms between biomarker profiles. RESULTS: Two profiles were identified and characterized based on decreases (profile 1: 67% female; age, 21.4 ± 5.1 years; body mass index, 24.4 ± 2.4) and increases (profile 2: 33% female; age, 21.3 ± 3.2 years; body mass index, 23.4 ± 2.6) in sMCP-1 and sCOMP preoperatively to 6 months after ACLR. Participants with profile 2 did not demonstrate differences in knee pain, symptoms, activities of daily living, sports function, or quality of life at 12 months after ACLR compared to those with profile 1 (P = .56-.81; η2 = 0.002-0.012). No statistically significant associations were noted between biomarker profiles and clinically relevant PTOA-related symptoms (odds ratio, 1.30; 95% CI, 0.23-6.33). CONCLUSION: Serum biomarker changes in MCP-1 and sCOMP within the first 6 months after ACLR were not associated with clinically relevant PTOA-related symptoms.
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Reconstrucción del Ligamento Cruzado Anterior , Biomarcadores , Cartílago Articular , Osteoartritis de la Rodilla , Humanos , Biomarcadores/sangre , Femenino , Masculino , Estudios de Casos y Controles , Adulto , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangre , Cartílago Articular/metabolismo , Adulto Joven , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicaciones , Lesiones del Ligamento Cruzado Anterior/sangre , Proteína de la Matriz Oligomérica del Cartílago/sangre , Quimiocina CCL2/sangre , Inflamación/sangre , Metaloproteinasa 3 de la Matriz/sangre , Articulación de la Rodilla/cirugía , Adolescente , Traumatismos de la Rodilla/cirugía , Traumatismos de la Rodilla/sangre , Traumatismos de la Rodilla/complicaciones , Colágeno Tipo II/sangreRESUMEN
Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.
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Biomarcadores , Quimiocinas , Osteoartritis de la Rodilla , Resistina , Líquido Sinovial , Ultrasonografía , Humanos , Resistina/sangre , Femenino , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/sangre , Proyectos Piloto , Biomarcadores/sangre , Quimiocinas/sangre , Líquido Sinovial/metabolismo , Índice de Severidad de la Enfermedad , Sedimentación Sanguínea , Articulación de la Rodilla/diagnóstico por imagen , Estudios de Casos y Controles , Anciano , Factor de Necrosis Tumoral alfa/sangre , Ácido Úrico/sangre , Interleucina-6/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismoRESUMEN
PURPOSE: This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders. MATERIALS AND METHODS: Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity. RESULTS: The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p<0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p=0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [ß, -1.923; standard error, 0.478; p<0.001 for men and ß, -1.532; SE, 0.575; p=0.008 for women]. CONCLUSION: Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA.
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Creatinina , Osteoartritis de la Rodilla , Humanos , Masculino , Femenino , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/diagnóstico por imagen , Creatinina/sangre , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Transversales , Anciano , Insuficiencia Renal/sangre , Modelos Logísticos , Índice de Severidad de la Enfermedad , Encuestas Nutricionales , Curva ROC , Pueblos del Este de AsiaRESUMEN
The controversy surrounding whether serum total cholesterol is a risk factor for the graded progression of knee osteoarthritis (KOA) has prompted this study to develop an authentic prediction model using a machine learning (ML) algorithm. The objective was to investigate whether serum total cholesterol plays a significant role in the progression of KOA. This cross-sectional study utilized data from the public database DRYAD. LASSO regression was employed to identify risk factors associated with the graded progression of KOA. Additionally, six ML algorithms were utilized in conjunction with clinical features and relevant variables to construct a prediction model. The significance and ranking of variables were carefully analyzed. The variables incorporated in the model include JBS3, Diabetes, Hypertension, HDL, TC, BMI, SES, and AGE. Serum total cholesterol emerged as a significant risk factor for the graded progression of KOA in all six ML algorithms used for importance ranking. XGBoost algorithm was based on the combined best performance of the training and validation sets. The ML algorithm enables predictive modeling of risk factors for the progression of the KOA K-L classification and confirms that serum total cholesterol is an important risk factor for the progression of KOA.
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Colesterol , Progresión de la Enfermedad , Aprendizaje Automático , Osteoartritis de la Rodilla , Humanos , Colesterol/sangre , Osteoartritis de la Rodilla/sangre , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Estudios Transversales , Anciano , AlgoritmosRESUMEN
This study aimed to examine dietary antioxidant and serum antioxidant capacity in patients with knee osteoarthritis (OA). This case-control study consisted of 47 patients with OA (case group) and 30 healthy subjects (control group). The control and case group were matched age, gender, and body mass index (p > 0.05). A food frequency questionnaire was administered to participants, and dietary total antioxidant capacity (DTAC) was estimated using the ferric reducing antioxidant power method (FRAP). Participants' serum total antioxidant capacity (TAC) and total oxidant capacity (TOC) measurements were performed, and the oxidative stress index (OSI) was calculated. DTAC of case group was found to be lower than the control group (p < 0.05). The daily consumption of red meat and butter of the individuals in the case group was higher than that of the control group, and their fish consumption, dietary vitamin A and carotene intakes were found to be lower (p < 0.05). In addition, OA patients have TAC and OSI was also found to be significantly higher than in control group (p = 0.001 and p < 0.001). Since low dietary total antioxidant capacity and high serum total oxidant capacity, individuals with OA should pay more attention to their diet to increase serum antioxidant status.
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Antioxidantes , Dieta , Osteoartritis de la Rodilla , Estrés Oxidativo , Humanos , Estudios de Casos y Controles , Femenino , Masculino , Antioxidantes/metabolismo , Antioxidantes/análisis , Persona de Mediana Edad , Osteoartritis de la Rodilla/sangre , Anciano , Índice de Masa CorporalRESUMEN
Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.
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Catepsinas , Análisis de la Aleatorización Mendeliana , Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Cadera/genética , Osteoartritis de la Cadera/sangre , Osteoartritis de la Cadera/diagnóstico , Catepsinas/sangre , Catepsinas/genética , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/diagnóstico , Predisposición Genética a la Enfermedad , Femenino , Masculino , Polimorfismo de Nucleótido Simple , Biomarcadores/sangreRESUMEN
BACKGROUND: The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10-15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1ß on Osteoarthritis risk is needed. METHODS: Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments. FINDINGS: Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1ß concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1ß when comparing baseline and post walking stimulus conditions. INTERPRETATION: The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development.
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Reconstrucción del Ligamento Cruzado Anterior , Citocinas , Articulación de la Rodilla , Humanos , Masculino , Femenino , Citocinas/sangre , Adulto , Articulación de la Rodilla/fisiopatología , Marcha , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Soporte de Peso , Interleucina-1beta/sangre , Caminata , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/cirugía , Fenómenos Biomecánicos , Biomarcadores/sangre , Estrés Mecánico , Ligamento Cruzado Anterior/cirugíaRESUMEN
BACKGROUND: Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA. METHODS: All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c. RESULTS: Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038). CONCLUSIONS: This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m 2 . These findings may help surgeons risk-stratify this high-risk patient population. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Obesidad Mórbida , Infecciones Relacionadas con Prótesis , Humanos , Femenino , Masculino , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Cadera/efectos adversos , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/sangre , Persona de Mediana Edad , Anciano , Infecciones Relacionadas con Prótesis/sangre , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/diagnóstico , Estudios Retrospectivos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangre , Factores de Riesgo , Periodo Preoperatorio , Recuento de Plaquetas , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Previously, fragments from Sirtuin 1 (SIRT1) were identified in preclinical and clinical samples to display an increase in serum levels for N-terminal (NT) SIRT1 vs. C-terminal (CT) SIRT1, indicative of early signs of OA. Here we tested NT/CT SIRT1 levels as well as a novel formulated sandwich assay to simultaneously detect both domains of SIRT1 in a manner that may inform us about the levels of full-length SIRT1 in the circulation (flSIRT1) of clinical cohorts undergoing knee joint distraction (KJD). METHODS: We employed an indirect ELISA assay to test NT- and CT-SIRT1 levels and calculated their ratio. Further, to test flSIRT1 we utilized novel antibodies (Ab), which were validated for site specificity and used in a sandwich ELISA method, wherein the CT-reactive served as capture Ab, and its NT-reactive served as primary detection Ab. This method was employed in human serum samples derived from a two-year longitudinal study of KJD patients. Two-year clinical and structural outcomes were correlated with serum levels of flSIRT1 compared to baseline. RESULTS: Assessing the cohort, exhibited a significant increase of NT/CT SIRT1 serum levels with increased osteophytes and PIIANP/CTX-II at baseline, while a contradictory increase in NT/CT SIRT1 was associated with less denuded bone, post-KJD. On the other hand, flSIRT1 exhibited an upward trend in serum level, accompanied by reduced denuded bone for 2-year adjusted values. Moreover, 2 year-adjusted flSIRT1 levels displayed a steeper linear regression for cartilage and bone-related structural improvement than those observed for NT/CT SIRT1. CONCLUSIONS: Our data support that increased flSIRT1 serum levels are a potential molecular endotype for cartilage-related structural improvement post-KJD, while NT/CT SIRT1 appears to correlate with osteophyte and PIIANP/CTX-II reduction at baseline, to potentially indicate baseline OA severity.
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Osteoartritis de la Rodilla , Sirtuina 1 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Cartílago Articular/patología , Cartílago Articular/metabolismo , Ensayo de Inmunoadsorción Enzimática , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Estudios Longitudinales , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/cirugía , Sirtuina 1/sangreRESUMEN
BACKGROUND: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. METHODS: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. RESULTS: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. CONCLUSIONS: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.
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Citocinas , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Polimorfismo de Nucleótido Simple/genética , Citocinas/sangre , Citocinas/genética , Femenino , Masculino , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Cadera/genética , Osteoartritis de la Cadera/sangre , Osteoartritis/genética , Osteoartritis/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Persona de Mediana Edad , Finlandia/epidemiologíaRESUMEN
Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is continuously targeting people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to analyze specific biomarkers, namely ACRP-30, IL-10, TNF-α, and IL-6, in knee synovial fluid, and correlate them with KOA patients' clinical data, radiographic changes, and functional and pain scores. Materials and Methods: 24 subjects with KOA and over 50 years of age participate in the present study. Synovial fluid was harvested using ultrasound guidance from the target knees of the enrolled KOA patients, and the levels of ACRP-30, IL-10, TNF-α, and IL-6 were measured using enzyme-linked immunosorbent assays (ELISA). All patients underwent a supine X-ray at the target knee and were classified using Kellgren-Lawrence (K-L) grading. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p = 0.0451, r = -0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p = 0.0405, r = -0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p = 0.0079, r = 0.7993), compared to women (p = 0.0203, r = 0.6223). In the case of women, the progression of the disease tends to increase more intensively the WOMAC score's total values (p = 0.00031, r = 0.8342), compared with men (p = 0.0289, r = 7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI; in addition, women seem to be more sensitive to pain and stiffness.
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Adiponectina , Biomarcadores , Citocinas , Interleucina-10 , Osteoartritis de la Rodilla , Factor de Necrosis Tumoral alfa , Humanos , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Adiponectina/sangre , Adiponectina/análisis , Anciano , Citocinas/sangre , Citocinas/análisis , Biomarcadores/análisis , Biomarcadores/sangre , Interleucina-10/sangre , Interleucina-10/análisis , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangre , Interleucina-6/sangre , Interleucina-6/análisis , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
OBJECTIVE: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up. METHOD: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry. Associations were measured by linear regression and receiver operating characteristics (ROC). RESULTS: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (ß(95% confidence intervals (CI)) = 1.809 (-0.71 to 2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (ß(95%CI) = 0.827 (0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (HETE) (ß(95%CI) = 4.090 (1.92-6.26)) and anandamide (ß(95%CI) = 3.060 (1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (numerical rating scale (NRS) item 3, average pain). Serum levels of 9- (ß(95%CI) = 0.467 (0.18-0.75)) and 15-HETE (ß(95%CI) = 0.759 (0.29-1.22)), 14-hydroxydocosahexaenoic acid (ß(95%CI) = 0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (ß(95%CI) = 0.510(0.19-0.82)) were cross-sectionally associated with KL scores. Baseline serum concentrations of 8,9-EET (ß(95%CI) = 2.166 (0.89-3.44)), 5,6-DHET (ß(95%CI) = 152.179 (69.39-234.97)), and 5-HETE (ß(95%CI) = 1.724 (0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (ß(95%CI) = 1.156 (0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (area under curve (95%CI) = 0.71 (0.61-0.82)). CONCLUSIONS: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.
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Artralgia , Progresión de la Enfermedad , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/sangre , Persona de Mediana Edad , Estudios Transversales , Anciano , Artralgia/sangre , Estudios Longitudinales , Estudios de Cohortes , Oxilipinas/sangre , Articulación de la Rodilla , Ácidos Hidroxieicosatetraenoicos/sangre , Ácidos Araquidónicos/sangre , Biomarcadores/sangre , Dimensión del Dolor , Ácido Araquidónico/sangreRESUMEN
OBJECTIVE: The objective was to determine whether baseline fatty acid intake and erythrocyte omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can predict risk of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older women. METHODS: This was a prospective analysis of 34,990 women in the Women's Health Initiative. Dietary fatty acids were estimated from food frequency questionnaires. Imputed erythrocyte PUFAs were available in a subcohort of 3,428 women. Arthroplasty (THA and TKA), used as a surrogate of severe osteoarthritis, was identified via linked Medicare data. Cox proportional hazards models were constructed to estimate risk of arthroplasty. RESULTS: Risk of THA was associated with higher intake of arachidonic acid, (multivariable hazard ratio [HR] quartile 4 [Q4] vs Q1: 1.16; 95% confidence interval [CI] 1.01-1.34; P = 0.03) and higher intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; HR Q4 vs Q1: 1.20; 95% CI 1.05-1.39; P = 0.003). There was a linear trend (P = 0.04) for patients to have a higher risk of THA with higher erythrocyte EPA and DHA in body mass index-adjusted models; however, there was no significant difference in patients who had THAs by quartiles of erythrocyte EPA and DHA (P = 0.10). Dietary fatty acids and erythrocyte PUFAs were not significantly associated with risk of TKA. CONCLUSION: Higher baseline intakes of arachidonic acid and EPA and DHA were associated with a modestly higher risk of THA. No association was found between fatty acids and patients who had TKAs. Further research in populations with direct measures of osteoarthritis severity is needed to better understand the importance of PUFAs in modulating osteoarthritis and arthroplasty risk.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Biomarcadores , Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Salud de la Mujer , Humanos , Femenino , Artroplastia de Reemplazo de Cadera/efectos adversos , Anciano , Estudios Prospectivos , Biomarcadores/sangre , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/sangre , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/sangre , Factores de Riesgo , Eritrocitos/química , Eritrocitos/metabolismo , Ácidos Grasos Omega-6/sangre , Ácidos Grasos Insaturados/sangre , Estados Unidos/epidemiología , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/administración & dosificación , Medición de RiesgoRESUMEN
OBJECTIVE: Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. METHODS: We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. RESULTS: We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. CONCLUSION: We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.
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Imagen por Resonancia Magnética , Osteoartritis de la Rodilla , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/epidemiología , Persona de Mediana Edad , Anciano , Factores de Riesgo , Articulación de la Rodilla/diagnóstico por imagen , Ácidos Grasos Omega-3/sangre , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Esenciales/sangre , Incidencia , Estados Unidos/epidemiología , Biomarcadores/sangre , Ácidos Grasos Omega-6/sangreRESUMEN
Background: This study aimed to quantify the mechanoresponse of 10 blood marker candidates for joint metabolism to a walking stress test in patients with knee osteoarthritis and to determine the association among marker kinetics and with accumulated load and patient reported outcomes. Methods: 24 patients with knee osteoarthritis completed questionnaires, and a 30-minute walking stress test with six blood serum samples and gait analysis. Concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases (MMP)-1, -3, and -9, epitope resulting from cleavage of type II collagen by collagenases (C2C), type II procollagen (CPII), interleukin (IL)-6, proteoglycan (PRG)-4, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and resistin were determined by enzyme-linked immunosorbent assays, Joint load (moments and compartmental forces) was estimated using musculoskeletal modeling using gait analysis data. Results: COMP and MMP-3 showed an immediate increase after the walking stress followed by a decrease. MMP-9 and resistin showed a delayed decrease below pre-stress levels. ∆COMP correlated with ∆MMP-3 for most time points. ∆MMP-9 correlated with ∆resistin for most time points. The load-induced increase in blood marker levels correlated among blood markers and time points. C2C and resistin correlated positively and C2C/CPII and MMP2 correlated negatively with load during gait. Immediate relative ∆CPII and ∆MMP1 and delayed relative ∆COMP, ∆IL6, ∆C2C, ∆CPII, ∆MMP1 and ∆MMP3 correlated with the load accumulated during the walking stress. Baseline C2C levels correlated with Knee Osteoarthritis Outcome Score (KOOS) subscales and load-induced changes in MMP-3 with KOOS and Short Form 36 quality of life subscores (P<0.05). Conclusions: The distinct and differentiated physiological response to the walking stress depends on accumulated load and appears relevant for patient reported osteoarthritis outcome and quality of life and warrants further investigation in the context of disease progression.ClinicalTrials.gov registration: NCT02622204.
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Biomarcadores , Osteoartritis de la Rodilla , Medición de Resultados Informados por el Paciente , Humanos , Femenino , Masculino , Osteoartritis de la Rodilla/sangre , Osteoartritis de la Rodilla/fisiopatología , Biomarcadores/sangre , Persona de Mediana Edad , Anciano , Cinética , Soporte de Peso , CaminataRESUMEN
OBJECTIVE: To investigate the effects of clearing heat and dispelling paralysis soup for osteoarthritis of the knee joint on the motor function of the knee joint and the level of inflammation of the organism in patients. METHODS: One hundred and sixteen patients with knee osteoarthritis admitted from January 2020 to May 2021 were selected and randomly divided into 2 groups, 58 cases in the control group were treated with loxoprofen sodium dispersible tablets, and 58 cases in the experimental group were treated with Qinghe dispel paralysis soup on the basis of the control group and the patients' balance ability analysis, gait parameter change analysis, VAS, JOA, AIMS2-SF scale assessment, and serum index. The treatment effects of the two treatment regimens were analyzed by testing. RESULTS: The anterior-posterior axis, left-right axis, A2-A6, A4-A8, and circumferential axis of the experimental group were lower than those of the control group after treatment (P < 0.05); the step length of the experimental group was higher than that of the control group after treatment (P < 0.05), and there were no significant differences in step speed, double-support phase, and step width (P > 0.05), but both groups improved significantly compared with those before treatment (P < 0.05); the VAS score of the experimental group was lower than that of the control group after treatment. The VAS scores of the experimental group were lower than those of the control group, and the scores of JOA and AIMS2-SF were higher than those of the control group (P < 0.05); the levels of TIMP-1 in the experimental group were higher than those in the control group, and the levels of TNF-α, TLR4, MMP-3, and IL-1 were lower than those in the control group after treatment (P < 0.05); there was no significant difference in the incidence of adverse reactions between the two groups during treatment (P > 0.05), and the efficiency of the experimental group was higher than that of the control group (P < 0.05). CONCLUSION: Combined treatment with Qinghe dispel paralysis soup can better promote the recovery of balance, improve motor ability, and reduce the development of inflammation in the organism, with high safety and effectiveness.