Clusterin Is Associated with Systemic and Synovial Inflammation in Knee Osteoarthritis

Cartilage ◽  
2020 ◽  
pp. 194760352095814
Author(s):  
Tachatra Ungsudechachai ◽  
Sittisak Honsawek ◽  
Jiraphun Jittikoon ◽  
Wanvisa Udomsinprasert
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Mrna Expression ◽  
Early Stage ◽  
Characteristic Curve ◽  
Synovial Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Knee Oa ◽  
Protein Levels ◽  
Synovial Tissues

Objectives This study aimed to determine possible associations between transcriptional and translational levels of clusterin (CLU) in the systemic and local joint environments with the severity of knee osteoarthritis (OA) and to investigate CLU mRNA expression in knee OA fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor-α. Design Circulating and synovial fluid CLU levels in 259 knee OA patients were quantified using an enzyme-linked immunosorbent assay. Relative CLU mRNA expression in 50 knee OA synovial tissues and 4 knee OA FLSs was determined using real-time polymerase chain reaction. Results Plasma CLU levels of knee OA patients were significantly higher than paired synovial fluid samples. Compared with early-stage knee OA patients, those with advanced-stage OA had considerably increased plasma and synovial fluid CLU levels. There were significant positive associations of plasma and synovial fluid CLU levels with radiographic severity of knee OA. Plasma CLU levels were directly correlated with its synovial fluid levels and high-sensitivity C-reactive protein levels in the patients. Receiver-operating characteristic curve analysis unveiled the potential utility of plasma CLU as a novel biomarker for knee OA severity (AUC = 0.80), with a sensitivity of 71.4% and a specificity of 73.3%. Marked upregulation of CLU mRNA expression was observed in both the inflamed synovial tissues and FLSs of knee OA. Conclusion Increased CLU mRNA and protein levels in the systemic and local joint environments of knee OA might reflect knee OA severity, especially systemic and synovial inflammation.

scholarly journals Diagnostic Value of Interleukin-34 as a Novel Biomarker for Severity of Knee Osteoarthritis

Cartilage ◽  
2021 ◽  
pp. 194760352199086
Author(s):  
Wanvisa Udomsinprasert ◽  
Kittaporn Panon ◽  
Siraphop Preechanukul ◽  
Jiraphun Jittikoon ◽  
Artit Jinawath ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Radiographic Severity ◽  
Knee Oa ◽  
Protein Expressions ◽  
Polymerase Chain ◽  
Synovial Tissues

Objectives This study aimed to determine whether plasma and synovial fluid interleukin-34 (IL-34), an inflammatory cytokine reportedly implicated in synovial inflammation-induced joint degeneration, were associated with radiographic severity of knee osteoarthritis (OA) patients and could emerge as knee OA biomarkers. Design Ninety-six knee OA patients and 72 healthy controls were recruited. Plasma and synovial fluid IL-34 levels were quantified using ELISA. IL-34 mRNA and protein expressions in inflamed ( n = 15) and noninflamed synovial tissues ( n = 15) of knee OA patients were determined using real-time polymerase chain reaction and immunohistochemistry, respectively. Results Significant increases in plasma and synovial fluid IL-34 levels were found in knee OA patients—especially those with advanced stage ( P < 0.001, P < 0.001, respectively). Both plasma and synovial fluid IL-34 levels were positively associated with radiographic severity ( r = 0.64, P < 0.001; r = 0.50, P < 0.001, respectively). There was a direct link between plasma and synovial fluid IL-34 ( r = 0.64, P < 0.001). Receiver operating characteristic curve analysis uncovered that the optimal cutoff value of plasma IL-34 as a novel biomarker reflecting knee OA severity was defined at 3750.0 pg/mL (AUC = 0.85), with a sensitivity of 83.1% and a specificity of 74.2%. Further analysis revealed that IL-34 mRNA expression was significantly upregulated in inflamed synovium compared with noninflamed synovium obtained from knee OA patients ( P < 0.001), consistent with protein expression analysis demonstrating IL-34 overexpression localized in the lining and sublining layers of inflamed synovium. Conclusions All findings suggest that elevated plasma and synovial fluid IL-34 would reflect knee OA severity and might have potential utility as biomarkers for the disease progression.

scholarly journals Diagnosis of early stage knee osteoarthritis based on early clinical course: data from the CHECK cohort

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Qiuke Wang ◽  
Jos Runhaar ◽  
Margreet Kloppenburg ◽  
Maarten Boers ◽  
Johannes W. J. Bijlsma ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Clinical Course ◽  
Early Stage ◽  
Characteristic Curve ◽  
Estimating Equation ◽  
Knee Oa ◽  
Diagnostic Models ◽  
Discriminative Value ◽  
Baseline Factors

Abstract Background Early diagnosis of knee osteoarthritis (OA) is important in managing this disease, but such an early diagnostic tool is still lacking in clinical practice. The purpose of this study was to develop diagnostic models for early stage knee OA based on the first 2-year clinical course after the patient’s initial presentation in primary care and to identify whether these course factors had additive discriminative value over baseline factors. Methods We extracted eligible patients’ clinical and radiographic data from the CHECK cohort and formed the first 2-year course factors according to the factors’ changes over the 2 years. Clinical expert consensus-based diagnosis, which was made via evaluating patients’ 5- to 10-year follow-up data, was used as the outcome factor. Four models were developed: model 1, included clinical course factors only; model 2, included clinical and radiographic course factors; model 3, clinical baseline factors + clinical course factors; and model 4, clinical and radiographic baseline factors + clinical and radiographic course factors. All the models were built by a generalized estimating equation with a backward selection method. Area under the receiver operating characteristic curve (AUC) and its 95% confidence interval (CI) were calculated for assessing model discrimination. Delong’s method compared AUCs. Results Seven hundred sixty-one patients with 1185 symptomatic knees were included in this study. Thirty-seven percent knees were diagnosed as OA at follow-up. Model 1 contained 6 clinical course factors; model 2: 6 clinical and 3 radiographic course factors; model 3: 6 baseline clinical factors combined with 5 clinical course factors; and model 4: 4 clinical and 1 radiographic baseline factors combined with 5 clinical and 3 radiographic course factors. Model discriminations are as follows: model 1, AUC 0.70 (95% CI 0.67–0.74); model 2, 0.74 (95% CI 0.71–0.77); model 3, 0.77 (95% CI 0.74–0.80); and model 4, 0.80 (95% CI 0.77–0.82). AUCs of model 3 and model 4 were slightly but significantly higher than corresponding baseline-factor models (model 3 0.77 vs 0.75, p = 0.031; model 4 0.80 vs 0.76, p = 0.003). Conclusions Four diagnostic models were developed with “fair” to “good” discriminations. First 2-year course factors had additive discriminative value over baseline factors.

scholarly journals Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis

2011 ◽  
Vol 34 (5) ◽  
pp. 298 ◽  
Author(s):  
Zhan-Chun Li ◽  
Guang-Qi Cheng ◽  
Kong-Zu Hu ◽  
Mao-Qiang Li ◽  
Wei-Ping Zang ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Disease Severity ◽  
Multinomial Logistic Regression ◽  
High Mobility ◽  
Enzyme Linked Immunosorbent Assay ◽  
Grading System ◽  
Radiographic Severity ◽  
Knee Oa ◽  
Radiographic Disease

Purpose: This study measured high-mobility group box 1 (HMGB-1) levels in serum and synovial fluid (SF) in patients with primary knee osteoarthritis (OA) and correlated these levels with radiographic disease severity. Methods: Seventy-eight OA patients and 30 controls were enrolled in this study. All OA patients were scored according to the Kellgren-Lawrence (KL) grading system. HMGB-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: SF HMGB-1 levels were significantly higher in knee OA patients, compared with controls (P < 0.01). Moreover, SF HMGB-1 levels were positively associated with KL scores (P < 0.01). Multinomial logistic regression demonstrated that the SF HMGB-1 level was an independent factor for radiographic severity of OA (P=0.002); however, serum HMGB-1 levels did not differ significantly between OA patients and controls and did not correlate with KL scores (P > 0.05). Conclusion: These results demonstrate that HMGB-1 levels in SF of knee OA patients are independently associated with radiographic disease severity.

scholarly journals Cartilage oligomeric matrix protein as a marker of progressive liver fibrosis in biliary atresia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wanvisa Udomsinprasert ◽  
Napat Angkathunyakul ◽  
Jiraphun Jittikoon ◽  
Usa Chaikledkaew ◽  
Paisarn Vejchapipat ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Biliary Atresia ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Early Stage ◽  
Characteristic Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Protein Levels ◽  
Protein Expressions

AbstractThis 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.

scholarly journals Circulating and Synovial Fluid Heat Shock Protein 70 Are Correlated with Severity in Knee Osteoarthritis

Cartilage ◽  
2018 ◽  
Vol 11 (3) ◽  
pp. 323-328
Author(s):  
Srihatach Ngarmukos ◽  
Shaun Scaramuzza ◽  
Nipaporn Theerawattanapong ◽  
Aree Tanavalee ◽  
Sittisak Honsawek
Keyword(s):  
Heat Shock ◽  
Synovial Fluid ◽  
Heat Shock Protein ◽  
Knee Osteoarthritis ◽  
Structural Integrity ◽  
Joint Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Radiographic Severity ◽  
Knee Oa ◽  
Shock Proteins

Objective Heat shock proteins are molecules rapidly produced under conditions of environmental stress, and involve in protecting the cells structural integrity and function. Osteoarthritis (OA) is a chronic destructive disorder of the joints manifested by the ongoing deterioration and loss of articular cartilage. The present study aimed to analyze circulating and synovial heat shock protein (Hsp70) values in knee osteoarthritis patients and healthy controls and to determine their relationship with the radiographic grading of the severity of knee OA. Design Seventy-two subjects with knee OA and 30 control participants were recruited. Circulating and joint fluid Hsp70 values were quantified by commercially available enzyme-linked immunosorbent assay. Results Circulating Hsp70 was markedly higher in knee OA patients compared with that of healthy volunteers ( P = 0.01). Correspondingly, synovial fluid Hsp70 was 3-fold greater than paired circulating Hsp70 samples ( P < 0.001). Further analysis revealed that circulating and joint fluid Hsp70 values were significantly related with the radiographic severity of knee OA ( r = 0.413, P < 0.001 and r = 0.658, P < 0.001, respectively). Subsequently, circulating Hsp70 value was directly associated with joint fluid Hsp70 value ( r = 0.704, P < 0.001). Conclusions Circulating and synovial Hsp70 levels were positively correlated with the radiographic severity of knee OA. Hsp70 could represent a potential biochemical marker for predicting the severity and may play a fundamental part in the pathogenic mechanism of knee OA.

scholarly journals Interleukin-34 Synovial Fluid Was Associated with Knee Osteoarthritis Severity: A Cross-Sectional Study in Knee Osteoarthritis Patients in Different Radiographic Stages

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Shuang-Lei Wang ◽  
Rui Zhang ◽  
Kong-Zu Hu ◽  
Mao-Qiang Li ◽  
Zhan-Chun Li
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Crucial Role ◽  
Proinflammatory Cytokine ◽  
Cross Sectional Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Confounding Factors ◽  
Sectional Study ◽  
Cross Sectional ◽  
Knee Oa

Background. Inflammation might play a crucial role in the pathogenesis of osteoarthritis (OA). Interleukin-34 (IL-34) is a well-known proinflammatory cytokine. Objective. The objective of this study was to detect IL-34 levels in serum and synovial fluid (SF) of patients with OA and to investigate their correlation with radiographic and symptomatic severity. Methods. One hundred and eighty-two OA patients and 69 controls were recruited. IL-34 levels were measured by enzyme-linked immunosorbent assay (ELISA). Radiographic and symptomatic severity of OA was reflected by Kellgren-Lawrence (KL) grades and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores, respectively. Results. SF IL-34 levels were independently associated with the KL grade (B=0.273, 95% CI: 0.150–0.395; P<0.001). SF IL-34 levels were significantly correlated with WOMAC scores (r=0.265, 95% CI: 0.123–0.399; P<0.001). The correlation between SF IL-34 levels and WOMAC scores was still significant after adjusting for confounding factors (B=0.020, 95% CI: 0.001–0.038; P=0.035) in OA patients. Conclusions. We found that IL-34 levels in SF were significantly associated with the radiographic and symptomatic severity of knee OA.

scholarly journals Synovial Fluid Eotaxin-1 Levels May Reflect Disease Progression in Primary Knee Osteoarthritis Among Elderly Han Chinese: A Cross-Sectional Study

Cartilage ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 408-416 ◽  
Author(s):  
Bei Li ◽  
Yi-Li Zhang ◽  
Shou-Yi Yu
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Disease Progression ◽  
Disease Severity ◽  
Han Chinese ◽  
Clinical Severity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Knee Oa ◽  
Significant Difference

Objective The CC chemokine family member eotaxin-1, also named chemokine C-C motif ligand 11 (CCL11), has been detected in knee osteoarthritis (OA) and could induce breakdown of cartilage matrix. This study was performed to investigate the plasma and synovial fluid eotaxin-1 levels with the disease progression in elderly Han Chinese with primary knee OA. Design A total of 143 elderly primary knee OA patients and 135 healthy controls were enrolled in the study. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was performed to evaluate the clinical severity. The radiographic severity was assessed by Kellgren-Lawrence (K-L) grading. Plasma and synovial fluid (SF) eotaxin-1 levels were explored using enzyme-linked immunosorbent assay. The SF levels of matrix metalloproteinase–3 (MMP-3) and interleukin-6 (IL-6) were also examined. Results Elevated plasma eotaxin-1 levels were found in knee OA patients compared with healthy controls. Eotaxin-1 levels in SF of knee OA patients with K-L grade 4 were significantly elevated compared with those with K-L grades 2 and 3. Meanwhile, knee OA patients with K-L grade 3 had significantly increased SF levels of eotaxin-1 compared with those with K-L grade 2. Plasma eotaxin-1 levels in different K-L grading did not reach significant difference. Eotaxin-1 levels in SF of knee OA patients were significantly associated with disease severity evaluated by KL grading criteria. In addition, eotaxin-1 levels in SF were positively related to clinical severity illustrated by WOMAC as well as biochemical markers MMP-3 and IL-6. Conclusions Eotaxin-1 levels in SF instead of plasma, were independently and positively related to the disease severity in elderly knee OA patients. The inhibition of eotaxin-1 and its related signaling pathways may serve as a novel therapeutic approach for OA progression.

scholarly journals Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 989
Author(s):  
Dhanashri Ingale ◽  
Priya Kulkarni ◽  
Ali Electricwala ◽  
Alpana Moghe ◽  
Sara Kamyab ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Early Stage ◽  
Challenge Test ◽  
Degradation Process ◽  
Cartilage Degradation ◽  
Gene Expressions ◽  
Inflammatory Microenvironment ◽  
Protein Levels ◽  
Advanced Stages ◽  
Inflammatory Milieu

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

scholarly journals TheBDKRB2 +9/-9 Polymorphisms Influence Pro-Inflammatory Cytokine Levels in Knee Osteoarthritis by Altering TLR-2 Expression: Clinical and in Vitro Studies

2016 ◽  
Vol 38 (3) ◽  
pp. 1245-1256 ◽  
Author(s):  
Shuo Chen ◽  
Lei Zhang ◽  
Ruonan Xu ◽  
Yunfan Ti ◽  
Yunlong Zhao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Inflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Knee Oa ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Underlying Mechanisms

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.

Serum Calprotectin as a Blood-Based Biomarker for Monitoring Knee Osteoarthritis at Early but Not Late Stages

Cartilage ◽  
2020 ◽  
pp. 194760352096116
Author(s):  
Amin Safa ◽  
Abolfazl Bagherifard ◽  
Hamadalla Hadi Al-Baseesee ◽  
Azade Amini Kadijani ◽  
Hooman Yahyazadeh ◽  
...  
Keyword(s):  
Disease Duration ◽  
Early Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Knee Oa ◽  
Calprotectin Level ◽  
Healthy Control ◽  
Grade Ii ◽  
Late Stages

Objective The identification of early-stage osteoarthritis (OA) is crucial for the deceleration of its progression; however, no reliable biomarker is available for this purpose. The current study aimed to determine the role of serum calprotectin in the detection of early-stage knee OA. Design In a case-control study, serum samples were collected from 84 patients with primary bilateral knee OA and 52 healthy controls. The radiographic grading of knee OA was performed using the Kellgren-Lawrence classification system. Serum concentrations of calprotectin were measured using an enzyme-linked immunosorbent assay. Results The mean serum calprotectin level was 2908 ± 2516 ng/mL in OA patients and 901 ± 875 ng/mL in healthy control subjects ( P < 0.001). Mean serum calprotectin levels were significantly higher in the lower stages of OA: 3740 ± 2728 ng/mL in OA grade I, 3100 ± 2084 ng/mL in OA grade II, 2246 ± 1418 ng/mL in OA grade III, and 2035 ± 765 ng/mL in OA grade IV ( P = 0.047). Serum calprotectin levels were significantly higher in patients with a disease duration <42 months compared with those with a disease duration >42 months ( P = 0.043). Conclusion Serum calprotectin level increases significantly in the early stages of OA and shows a reverse association with disease severity. Therefore, it could be suggested as a promising blood-based marker for early-stage knee OA.

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