Synovial Fluid Of Knee Osteoarthritis Patients Research Articles

RAGE signalling contributes to oxidative stress and inflammation in knee osteoarthritis patients with metabolic syndrome.

Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO. This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome. We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well. We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.

Effect of hyaluronic acid on cytokines and immune cells change in patients of knee osteoarthritis

PurposeTo evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid(IAHA)injections in patients with knee osteoarthritis (KOA).Patients and MethodsSixteen patients were included in the study, with a total of 65 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined.ResultsIL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (< 2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8.ConclusionThe synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study partially revealed the effect of IAHA on cytokines and immune cells change in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain.Trial registrationChiCTR2100050133; date registered 17 August 2021.

Targeted phospholipidomic analysis of synovial fluid as a tool for osteoarthritis deep phenotyping

ObjectiveThe aim of this study was to carry out a targeted phospholipidomic analysis on synovial fluid (SF) from patients with different grades of osteoarthritis (OA) and controls, in order to search for specific phospholipid profiles that may be useful for the deep phenotyping of this disease. DesignMultiple reaction monitoring-mass spectrometry (MRM/MS) was applied to explore the potential phospholipidomic differences in the SF of knee OA patients (n ​= ​15) (subclassified into early- and late-stage OA) and non-OA controls (n ​= ​4). Multivariate statistical analyses conducted by partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) were performed to identify significantly altered phospholipids in OA, characterize phospholipidomic profiles associated with the radiographic stage of the disease and describe potential endotypes at early stages. ResultsSignificant discrimination of phospholipid profiles between non-OA controls and the early- and late-stage OA groups were found by PLS-DA and HCA. Compared to SF from non-OA controls, OA patients showed higher levels of most quantified phospholipid species, including phosphatidylcholines (PC), phosphatidylserines and phosphatidylinositols. Furthermore, several PC species showed significant differences in abundance between the two OA subgroups and were negatively correlated with cartilage damage. Finally, two distinct endotypes of early-stage OA were identified based on the phospholipidomic profile of SF. ConclusionsOur data provides a novel insight into the phospholipid profiles of OA synovial fluid, revealing specific alterations associated with the radiographic stage of the disease. This targeted phospholipidomic profiling also facilitated the characterization of two different OA endotypes at early stages of the disease.

CCL3/CCR1 mediates CD14+CD16− circulating monocyte recruitment in knee osteoarthritis progression

Monocyte-derived macrophages, as the predominant immune cell type that is increased in inflamed synovium, play a vital role during knee osteoarthritis (KOA) progression. However, the mechanisms underlying the recruitment of circulating monocytes to osteoarthritic knees remain uncertain. Based on previous data obtained from plasma, we investigated the contributions of CCL2, CCL3, CCL4 and their cognate receptors in circulating monocyte chemotaxis and KOA development. Using flow cytometry staining, we characterized the expression patterns of the chemokine receptors in CD14+CD16- circulating monocytes from KOA patients and healthy volunteers. The expression of chemokines in synovial fluids, synovium and cartilage was investigated in KOA patients and in patients without KOA. The role of chemokines and their cognate receptors in the chemotaxis of CD14+CD16- circulating monocytes was assessed using chemokine neutralizing antibodies (NA) and receptor antagonists in vitro and in vivo. The majority of CD14+CD16- circulating monocytes were CCR1-and CCR2-positive. CCL2, CCL3 and CCL4 were elevated in synovial fluid of KOA patients compared with that of controls. The most likely source of these chemokines is inflamed synovium and cartilage in the osteoarthritic knee. The CCL3/CCR1 and CCL2/CCR2 axes showed substantial ability to recruit CD14+CD16- monocytes in transwell assays. Similar results were confirmed in a mouse model of collagenase-induced KOA (CIA) in which blocking either the CCL3/CCR1 axis or the CCL2/CCR2 axis reduced synovial hyperplasia and F4/80+ macrophage infiltration. Our findings suggested that, analogous to the CCL2/CCR2 axis, CCL3 produced in osteoarthritic knees can chemoattract circulating monocytes to the inflamed synovium through CCR1.

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

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. 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. 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. 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.

Association of CCL13 Levels in Serum and Synovial Fluid With the Radiographic Severity of Knee Osteoarthritis

ObjectiveCCL13, a recently identified CC chemokine, plays an important role in the process of joint destruction, which is considered a common cause for osteoarthritis (OA). This study aims to examine...

Correlation of bone morphogenetic protein-2 levels in serum and synovial fluid with disease severity of knee osteoarthritis.

BackgroundThis study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease.Material/MethodsA total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay.ResultsSerum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores.ConclusionsBMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.

Association between hypoxia-inducible factor-1a levels in serum and synovial fluid with the radiographic severity of knee osteoarthritis.

Osteoarthritis (OA) is primarily characterized by articular cartilage degradation. Hypoxia-inducible factor-1a (HIF-1a), a subunit of the basic helix-loop-helix-containing PER-ARNT-SIM (PAS) domain transcription factors, plays a vital role in the survival of articular chondrocytes to the hostile hypoxic microenvironment and complicates the progression of OA. In this study, we examined whether HIF-1a levels in the serum and synovial fluid (SF) of patients with knee OA were increased and whether the increase was correlated with the radiographic severity of the disease. A total of 278 knee OA patients and 203 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed on anteroposterior knee radiography. HIF-1a levels in the serum and SF were determined using an enzyme-linked immunosorbent assay. Serum HIF-1a levels in patients with knee OA were higher than those in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated HIF-1a levels in the serum and SF compared with those with KL grades 2 and 3. Knee OA patients with KL grade 3 showed significantly higher SF levels of HIF-1a than those with KL grade 2. HIF-1a levels in the serum and SF of knee OA patients were significantly correlated with disease severity according to KL grading criteria. HIF-1a levels in the serum and SF were closely related to the radiographic severity of OA and may serve as an alternative biomarker for the progression and prognosis of knee OA.

Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis

Fractalkine has been detected in synovial fluid (SF) from osteoarthritis (OA) patients. This study aims to examine the relation of fractalkine concentrations in serum and SF with the radiographic severity of OA. Fractalkine concentrations of serum and SF were measured using an enzyme-linked immunosorbent assay method in 223 patients with knee OA and 165 healthy controls. The progression of OA was classified according to the Kellgren-Lawrence grading system. Elevated concentrations of fractalkine in serum were found in knee OA patients compared with healthy controls [all results median (interquartile range) 226.25 (183.19-259.91) vs. 127.42 (99.54-154.98) pg/mL, P < 0.001]. The case group included 71 knee OA patients with grade 2, 98 with grade 3, and 54 with grade 4. Knee OA patients with KL grade 4 had significantly higher fractalkine concentrations in serum and SF compared with those with KL grade 2 and 3 [serum: 247.68 (215.05-278.64) vs. 212.45 (169.19-247.96) pg/mL, P < 0.001, and 247.68 (215.05-278.64) vs. 222.00 (179.80-254.98) pg/mL, P = 0.005, respectively; SF: 94.95 (76.46-106.68) vs. 74.31 (63.64-84.79) pg/mL, P < 0.001, and 94.95 (76.46-106.68) vs. 80.34 (68.84-96.39) pg/mL, P = 0.001, respectively]. Knee OA patients with KL grade 3 showed significantly elevated concentrations of fractalkine in SF compared with those with KL grade 2 [80.34 (68.84-96.39) vs. 74.31 (63.64-84.79) pg/mL, P = 0.004]. Fractalkine concentrations in serum and SF of knee OA patients were both significantly associated with the disease severity evaluated by KL grading criteria (r = 0.261, P < 0.001 and r = 0.366, P < 0.001, respectively). The fractalkine concentrations in serum and SF may serve as an effective biomarker for the severity of OA.

Increased thymosin β4 levels in the serum and SF of knee osteoarthritis patients correlate with disease severity

ObjectiveThymosin β4, a member of a large family of thymic proteins, plays an important role in the process of articular cartilage degeneration which is a common cause of osteoarthritis (OA). This study aims to determine thymosin β4 levels in the serum and synovial fluid (SF) of patients with knee OA and analyze the correlation of thymosin β4 levels with the radiographic severity of OA. MethodsThis study consisted of 216 patients with knee OA and 152 healthy controls. OA progression was classified based on Kellgren–Lawrence by evaluating x-ray changes observed in anteroposterior knee radiography. Thymosin β4 levels in the serum and SF were measured by enzyme-linked immunosorbent assay method. ResultsThe knee OA patients had higher levels of serum thymosin β4 than the healthy controls. Knee OA patients with KL grade 4 showed significantly elevated thymosin β4 levels in the serum and SF compared with those with KL grades 2 and 3. Knee OA patients with KL grade 3 had significantly higher SF levels of thymosin β4 than those with KL grade 2. Thymosin β4 levels in the serum and SF of knee OA patients were significantly correlated with disease severity according to KL grading criteria. ConclusionThe thymosin β4 levels in the serum and SF may serve as effective biomarkers for the severity of OA.

Association of CXCL12 Levels in Synovial Fluid With the Radiographic Severity of Knee Osteoarthritis

ObjectiveInflammation is implicated to be involved in the pathogenesis of osteoarthritis (OA). CXCL12, also known as stromal cell-derived factor, is the unique identified natural ligand of the G-protein-coupled receptor CXCR4...

Association of MIF in serum and synovial fluid with severity of knee osteoarthritis

Recent evidences suggest that inflammation contributes to the development and progression of osteoarthritis (OA). This study aims to determine macrophage migration inhibitory factor (MIF) levels in serum and synovial fluid (SF) of patients with knee OA and to analyze the association of MIF levels with the radiographic severity of OA. 224 patients with knee OA and 186 healthy controls were enrolled in this study. Higher levels of serum MIF were found in knee OA patients compared with healthy controls. Knee OA patients with Kellgren and Lawrence (KL) grade 4 showed significantly elevated MIF levels in serum and SF compared with those with KL grade 2 and 3. MIF levels in serum and SF of knee OA patients were significantly related to disease severity evaluated by KL grading criteria. MIF levels in serum and SF were closely related to the radiographic severity of OA.

Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis

Context: Chemerin has been implicated to be correlated with inflammation.Objective: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA).Methods: 124 patients with knee OA and 76 healthy controls were enrolled in this study.Results: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria.Conclusion: Chemerin levels may be involved in the pathophysiology of the development and progression of OA.

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

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. 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). 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). These results demonstrate that HMGB-1 levels in SF of knee OA patients are independently associated with radiographic disease severity.