Association between Common Variants in VEGFA Gene and the Susceptibility of Primary Knee Osteoarthritis.

OBJECTIVES: This study aimed to analyze the relationship between vascular endothelial growth factor A (VEGFA) gene polymorphisms, plasma VEGFA, and the susceptibility of knee osteoarthritis (OA). DESIGN: A total of 404 subjects, 202 knee OA subjects and 202 healthy volunteers, were enrolled into the study. Four distinct polymorphisms of the VEGFA gene were evaluated using polymerase chain reaction-restriction fragment length polymorphism: -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039). Plasma VEGFA levels were analyzed using enzyme-linked immunosorbent assay. RESULTS: The most common nucleotides in both knee OA subjects and healthy controls were CC for -2578C/A, GG for -1154G/A, CG for -634C/G, and CC for +936C/T in the VEGFA gene. Genotype distribution and allele frequencies of VEGFA -2578C/A, -1154G/A, -634C/G, and +936C/T single nucleotide polymorphisms did not differ between OA patients and the controls. Plasma VEGFA levels showed no difference between OA patients and the controls. In contrast, plasma VEGFA levels of -634C/C genotype were significantly higher in OA patients than in the controls (P = 0.035). According to the -2578A/A genotype, patients with early stage OA had a higher odds ratio than those with advanced stage OA (P = 0.023). CONCLUSIONS: VEGFA -2578C/A (rs699947), -1154G/A (rs1570360), -634C/G (rs2010963), and +936C/T (rs3025039) polymorphisms may not be responsible for OA susceptibility in the Thai population. However, the OA patients with A/A genotype at the -2578C/A seemed to have a lower potential risk of developing severe OA than those with the C/A and C/C genotypes. These findings would help elucidate and facilitate a better understanding of the genetic fundamentals of OA.

Association between leukocyte telomere length and angiogenic cytokines in knee osteoarthritis.

AIM: The aims of this study were to compare leukocyte relative telomere length (RTL) in knee osteoarthritis (OA) patients and healthy controls and to investigate associations between plasma angiogenic cytokine concentrations and leukocyte RTL. METHOD: Eighty knee OA patients and 60 age-matched controls were enrolled. Leukocyte RTL was assessed using real-time quantitative polymerase chain reaction (qPCR). Angiogenic cytokines were measured by a multiplex immunoassay. RESULTS: Leukocyte RTL in knee OA patients was significantly lower than that in healthy controls (1.1 ± 0.4 vs. 1.3 ± 0.6, P = 0.039). Plasma angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin-8 (IL-8), platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial growth factor (VEGF) levels in knee OA patients were higher than those in controls (P < 0.01). Correlation analysis revealed significant negative correlations between leukocyte RTL and plasma levels of HGF (r = -0.377, P = 0.017), VEGF (r = -0.405, P = 0.009) and G-CSF (r = -0.347, P = 0.026). In contrast, plasma angiopoietin-2, follistatin, IL-8, leptin, platelet-derived growth factor-BB and PECAM-1 were not correlated with leukocyte RTL. CONCLUSION: Telomere length was shortened in knee OA patients compared to healthy controls. Plasma HGF, VEGF and G-CSF were negatively correlated with leukocyte RTL, suggesting involvement of telomere shortening and these cytokines in knee OA.

Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis.

PURPOSE: The aim of this study was to compare angiogenic cytokine levels in knee osteoarthritis (OA) patients and healthy controls and to investigate the relationships between angiogenic cytokines and the OA severity. METHODS: Thirty-one knee OA patients and 15 healthy controls were recruited. Nine angiogenic cytokines (angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin (IL)-8, leptin, platelet-derived growth factor-BB (PDGF-BB), platelet endothelial cell adhesion molecule (PECAM)-1, and vascular endothelial growth factor (VEGF)) in plasma and synovial fluid were measured using a multiplex immunoassay. RESULTS: PECAM-1, HGF, VEGF, angiopoietin-2, follistatin, G-CSF, and IL-8 concentrations in plasma were significantly higher in OA patients than those in controls. Plasma angiopoietin-2 was significantly greater in advanced OA than in early OA. Synovial fluid VEGF was positively correlated with the severity (r = 0.367, P = 0.04). Plasma follistatin was significantly lower in advanced knee OA than in early OA and was negatively correlated with the severity (r = -0.374, P < 0.05). CONCLUSIONS: Angiogenic cytokine concentrations in plasma can distinguish between controls and OA patients. Local and circulating levels of angiogenic cytokines could give an insight into the pathophysiology of OA. Follistatin, angiopoietin-2, and VEGF may have potential as biochemical markers for the assessment of OA severity.

Plasma and synovial fluid sclerostin are inversely associated with radiographic severity of knee osteoarthritis.

OBJECTIVE: The purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity. DESIGN AND METHODS: A total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification. RESULTS: Plasma sclerostin levels were significantly lower in OA patients than in healthy controls (P=0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r=-0.464, P<0.001 and r=-0.592, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r=0.657, P<0.001). CONCLUSIONS: Sclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA.

Relationship of plasma and synovial fluid vascular endothelial growth factor with radiographic severity in primary knee osteoarthritis.

PURPOSE: Recent evidence suggests that angiogenesis and inflammation contribute to the development and progression of osteoarthritis (OA). The purpose of this study was to investigate vascular endothelial growth factor (VEGF) levels in plasma and synovial fluid of patients with knee OA and to determine the relationship of VEGF levels with disease severity in knee OA. METHODS: A total of 100 subjects were enrolled in this study (80 knee OA patients and 20 healthy controls). Plasma and synovial fluid VEGF levels were analysed using enzyme-linked immunosorbent assay. VEGF expressions in synovial membrane and articular cartilage samples were assessed using immunohistochemistry. RESULTS: VEGF level in synovial fluid of knee OA patients was tenfold higher than that in paired plasma (P < 0.001). Both plasma and synovial fluid VEGF exhibited a positive correlation with radiographic severity (r = 0.454 and r = 0.727, P < 0.001, respectively). VEGF expression was highly detectable in synovial lining cells and articular chondrocytes of knee OA patients. CONCLUSIONS: VEGF levels in both plasma and synovial fluid were positively correlated with the severity of knee OA. Therefore, VEGF may be useful for monitoring OA severity and could play a substantial role in the development and progression of knee OA.

Plasma and synovial fluid connective tissue growth factor levels are correlated with disease severity in patients with knee osteoarthritis.

BACKGROUND: Connective tissue growth factor (CTGF) has been implicated in development of osteoarthritis (OA). OBJECTIVE: To determine the correlation between plasma and synovial fluid CTGF levels and the severity in knee osteoarthritis patients. METHODS: A total of 100 subjects were recruited into this study (75 OA patients and 25 controls). CTGF concentrations in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. RESULTS: Plasma and synovial fluid CTGF concentrations were correlated with radiographic severity. There was a positive correlation between plasma and synovial fluid CTGF levels. CONCLUSION: CTGF could be useful for monitoring the severity and progression of OA.

Correlation between plasma and synovial fluid basic fibroblast growth factor with radiographic severity in primary knee osteoarthritis.

PURPOSE: The aim of this study was to investigate plasma and synovial fluid basic fibroblast growth factor (bFGF) levels in patients with primary knee osteoarthritis (OA) and to evaluate the correlation between bFGF levels and disease severity. METHODS: Thirty-five patients with knee OA and 15 healthy individuals were recruited into this study. Knee OA grading was performed according to the Kellgren-Lawrence classification. bFGF concentrations in both plasma and synovial fluid were determined using enzyme-linked immunosorbent assay. RESULTS: Plasma and synovial fluid bFGF levels in knee OA patients were significantly higher than in controls (P < 0.001). Moreover, plasma and synovial fluid bFGF concentrations were positively correlated with radiographic severity (r = 0.535, P < 0.001 and r = 0.570, P < 0.001, respectively). Further analysis revealed that there was a positive correlation between plasma and synovial fluid bFGF levels (r = 0.674, P < 0.001). CONCLUSIONS: Plasma and synovial fluid bFGF levels were significantly increased in OA patients, and these elevated levels were positively correlated with radiographic severity. These findings indicate that bFGF levels may be a monitor of disease severity and could play an essential part in the pathophysiology of degenerative process in OA.

Association of plasma and synovial fluid interferon-γ inducible protein-10 with radiographic severity in knee osteoarthritis.

OBJECTIVES: The objective of this study was to investigate interferon-γ inducible protein-10 (IP-10) concentrations in plasma and synovial fluid of patients with knee osteoarthritis (OA) and to analyze their relationship with disease severity. DESIGN AND METHODS: Forty OA patients and 15 healthy controls were enrolled in this study. OA grading was performed according to the Kellgren-Lawrence criteria. IP-10 levels in plasma and synovial fluid were assessed using enzyme-linked immunosorbent assay. RESULTS: Plasma IP-10 levels in the knee OA patients were significantly lower than those of controls (P=0.006). IP-10 levels in plasma were markedly higher with regard to paired synovial fluid (P<0.001). Furthermore, IP-10 concentrations in plasma and synovial fluid displayed significant inverse correlation with radiographic severity (r=-0.713, P<0.001 and r=-0.561, P<0.001, respectively). Subsequent analysis revealed that plasma IP-10 levels were positively correlated with synovial fluid IP-10 levels (r=0.424, P=0.006). CONCLUSIONS: IP-10 levels in both plasma and synovial fluid were inversely associated with the severity of knee OA. Accordingly, IP-10 could serve as a biomarker for determining disease severity and might play a possible role in the pathophysiology of osteoarthritis.

Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity. METHODS: Thirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay. RESULTS: The average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001). CONCLUSIONS: Dkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.