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

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.

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

Cartilage ◽

10.1177/1947603518790075 ◽

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.

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

Cartilage ◽

10.1177/1947603518764280 ◽

2018 ◽

Vol 10 (4) ◽

pp. 408-416 ◽

Cited By ~ 1

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.

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High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis

Cartilage ◽

10.1177/19476035211007919 ◽

2021 ◽

pp. 194760352110079

Author(s):

Kaibin Zhang ◽

Yisheng Ji ◽

Hanhao Dai ◽

Abdul Aleem Khan ◽

Yang Zhou ◽

...

Keyword(s):

Synovial Fluid ◽

Knee Osteoarthritis ◽

High Density Lipoprotein ◽

Disease Severity ◽

Cartilage Damage ◽

Density Lipoprotein ◽

Apolipoprotein A1 ◽

Lipoprotein Cholesterol ◽

Advanced Stage ◽

Radiographic Severity

Objectives The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. Materials and Methods The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. Results No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels ( P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores ( P < 0.05), which were still significant after adjusting for confounding factors ( P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA ( P < 0.001). Conclusion SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

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Clusterin Is Associated with Systemic and Synovial Inflammation in Knee Osteoarthritis

Cartilage ◽

10.1177/1947603520958149 ◽

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.

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The Relationship between Knee Adduction Moment and Knee Osteoarthritis Symptoms according to Static Alignment and Pelvic Drop

BioMed Research International ◽

10.1155/2019/7603249 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yong Nie ◽

Hua Wang ◽

Bin Xu ◽

ZongKe Zhou ◽

Bin Shen ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Linear Models ◽

Knee Adduction Moment ◽

Radiographic Severity ◽

Negatively Associated ◽

Knee Oa ◽

Symptomatic Knee ◽

Radiographic Disease ◽

The Relationship ◽

Hss Score

Objectives. To investigate the relationship between external knee adduction moment (KAM) and knee osteoarthritis (OA) symptoms according to static alignment and pelvic drop. Methods. Ninety-five participants with symptomatic knee OA were included. Radiographic severity was graded by Kellgren and Lawrence (KL) scale. The hip-knee-ankle (HKA) angle was used to assess limb alignment from a full-length lower-limb radiograph. KAM-related variables (peak KAM and KAM impulse) and pelvic drop angle were determined from 3D gait analysis. Symptoms were assessed via visual analog scale (VAS) for pain and hospital for special surgery (HSS) score for physical function. The relationship between KAM and symptoms was evaluated according to radiographic severity and pelvic drop using linear models. Results. According to the more affected knee in the varus group, both the two KAM-related measures (peak KAM and KAM impulse) were positively associated with greater VAS pain and were negatively associated with HSS score. Only peak KAM was correlated with VAS and HSS in the valgus group. VAS pain score of the more affected knee was positively correlated with pelvic drop angle. Stratified by pelvic drop angle, KAM-related variables were more positively associated with VAS pain and negatively associated with HSS score for patients with pelvic drop angle ≤3 degrees. The relationships between KAM and symptoms according to radiographic disease severity remained confusing. Conclusions. Static alignment and pelvic drop angle significantly affected relationships between KAM-related variables and knee OA symptoms, which may explain the confusing results as shown by previous studies.

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

Cartilage ◽

10.1177/1947603521990866 ◽

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.

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The Expression of Osteopontin and Wnt5a in Articular Cartilage of Patients with Knee Osteoarthritis and Its Correlation with Disease Severity

BioMed Research International ◽

10.1155/2016/9561058 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Yusheng Li ◽

Wenfeng Xiao ◽

Minghua Sun ◽

Zhenhan Deng ◽

Chao Zeng ◽

...

Keyword(s):

Articular Cartilage ◽

Knee Osteoarthritis ◽

Real Time ◽

Disease Severity ◽

Real Time Pcr ◽

Grading System ◽

Progressive Damage ◽

Knee Oa ◽

Wnt5a Expression ◽

Normal Controls

Objectives. This study is undertaken to investigate the relation between osteopontin (OPN) and Wnt5a expression in the progression and pathogenesis of osteoarthritis (OA).Methods. 50 cartilage tissues from knee OA patients and normal controls were divided into four groups of severe, moderate, minor, and normal lesions based on the modified grading system of Mankin. Immunohistochemistry and real-time PCR were utilized to analyze the OPN and Wnt5a expression in articular cartilage. Besides, the relations between OPN and Wnt5a expression and the severity of OA were explored.Results. OPN and Wnt5a could be identified in four groups’ tissues. Amongst the groups, the intercomparisons of OPN expression levels showed statistical differences (P<0.01). Besides, the intercomparisons of Wnt5a expression degrees showed statistical differences (P<0.05), except that between the minor and normal groups (P>0.05). The scores of Mankin were demonstrated to relate to OPN expression (r=-0.847,P<0.01) and Wnt5a expression in every group (r=-0.843,P<0.01). Also, a positive correlation can be observed between the OPN and Wnt5a expression (r=0.769,P<0.01).Conclusion. In articular cartilage, the expressions of OPN and Wnt5a are positively related to progressive damage of knee OA joint. The correlation between Wnt5a and OPN might be important to the progression and pathogenesis of knee OA.

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

Disease Markers ◽

10.1155/2018/2095480 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 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.

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