Sittisak Honsawek

Correlation of Plasma and Synovial Fluid Adiponectin with Knee Osteoarthritis Severity

BACKGROUND AND AIMS Osteoarthritis (OA) is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. The purposes of this study were to measure adiponectin concentrations in plasma and synovial fluid of patients with knee OA and to analyze the correlation of adiponectin levels with disease severity. METHODS Seventy six OA patients (mean age 69.8 ± 1.1 years) and 24 healthy controls (mean age 71.2 ± 1.5 years) were enrolled in this study. OA grading was performed using the Kellgren-Lawrence (KL) criteria by evaluating x-ray changes observed in anteroposterior knee radiography. Adiponectin levels in plasma and synovial fluid were determined by commercial enzyme-linked immunosorbent assay. RESULTS Plasma levels of adiponectin were higher in OA patients compared to healthy individuals, but the difference did not reach statistical significance (2428.0 ± 245.1 vs. 2030.3 ± 399.4 ng/mL, p = 0.4). Adiponectin levels in plasma were remarkably higher with regard to paired synovial fluid (2428.0 ± 245.1 vs. 301.3 ± 44.9 ng/mL, p <0.001). Additionally, adiponectin concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity evaluated by KL grading criteria (r = -0.68, p <0.001 and r = -0.47, p <0.001, respectively). Further analysis showed that plasma adiponectin levels positively correlated with synovial fluid adiponectin levels (r = 0.71, p <0.001). CONCLUSIONS Adiponectin levels in both plasma and synovial fluid decreased significantly as the severity of OA increased. These findings suggested that adiponectin may play a protective role in OA. More studies are warranted to gain insight into the potential utility of adiponectin as a biochemical determinant of disease progression and prognosis.

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

BackgroundOsteoarthritis (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.MethodsThirty-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.ResultsThe 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).ConclusionsDkk-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.

Correlation of plasma and synovial fluid osteopontin with disease severity in knee osteoarthritis

OBJECTIVES The purposes of this study were to examine osteopontin levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to investigate their relationship with severity of the disease. DESIGN AND METHODS Thirty-two patients aged 53-83 years with knee OA and 15 healthy controls were enrolled in this study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. Osteopontin levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. RESULTS The mean plasma osteopontin concentration of the knee OA patients was significantly higher compared with that of healthy controls (168.8+/-15.6 vs 67.2+/-7.7 ng/mL, P<0.0001). Osteopontin levels in synovial fluid were significantly higher with respect to paired plasma samples (272.1+/-15.0 vs 168.8+/-15.6 ng/mL, P<0.001). In addition, plasma osteopontin levels showed a positive correlation with synovial fluid osteopontin levels (r=0.373, P=0.035). Subsequent analysis showed that plasma osteopontin levels significantly correlated with severity of disease (r=0.592, P<0.001). Furthermore, the synovial fluid levels of osteopontin also correlated with disease severity (r=0.451, P=0.01). CONCLUSION The data suggest that osteopontin in plasma and synovial fluid is related to progressive joint damage in knee OA. Osteopontin may serve as a biochemical marker for determining disease severity and could be predictive of prognosis with respect to the progression of knee OA.

Cytokines as biochemical markers for knee osteoarthritis

Osteoarthritis (OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly being considered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and anti-inflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin (IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.

Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease most commonly occurring in the ageing population. It is a slow progressive condition resulting in the destruction of hyaline cartilage followed by pain and reduced activity. Conventional treatments have little effects on the progression of the condition often leaving surgery as the last option. In the last 10 years tissue engineering utilising mesenchymal stem cells has been emerging as an alternative method for treating OA. Mesenchymal stem cells (MSCs) are multipotent progenitor cells found in various tissues, most commonly bone marrow and adipose tissue. MSCs are capable of differentiating into osteocytes, adipocytes, and chondrocytes. Autologous MSCs can be easily harvested and applied in treatment, but allogenic cells can also be employed. The early uses of MSCs focused on the implantations of cell rich matrixes during open surgeries, resulting in the formation of hyaline-like durable cartilage. More recently, the focus has completely shifted towards direct intra-articular injections where a great number of cells are suspended and injected into affected joints. In this review the history and early uses of MSCs in cartilage regeneration are reviewed and different approaches in current trends are explained and evaluated.

Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament ruptures.

Anterior cruciate ligament (ACL) ruptures are considered to be the most severe joint injury in sports. However, the precise etiologies of ACL injuries are not fully understood. Recently, the gene encoding the matrix metalloproteinase-3 (MMP-3, stromelysin-1) was shown to be associated with anterior cruciate ligament ruptures. The 5A/6A polymorphism in the promoter of the MMP-3 gene affects the regulation of MMP-3 gene expression. We examined the association between polymorphism within -1612 of the MMP-3 gene and ACL rupture in an independent population. Eighty-six participants between 20 and 40 years of age with surgically diagnosed ACL ruptures and 100 healthy controls between 18 and 28 years of age without history of ligament or tendon injuries were recruited for the study. All participants were genotyped for the MMP-3 polymorphism (-1612 5A/6A). Statistical analyses of genotype frequencies between patients and healthy controls were performed by the chi-square test. A significant difference was found between ACL rupture subgroups in terms of genotype association (5A+ (5A/5A, 5A/6A): 37.5% in contact sports vs 20% in non-contact sports; P = 0.02). In allelic association, there were significant differences (6A: 81.2% in contact sports vs 89.1% in non-contact sports, 5A: 18.8% in contact sports vs 10.9% in non-contact sports, P = 0.01). The 5A+ genotype of MMP-3 was represented in ACL ruptures in contact sport participants. We propose that this sequence variant is a specific genetic element that should be included in a multifactorial model to understand the etiologies and risk factors for ACL rupture.

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

PurposeRecent 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.MethodsA 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.ResultsVEGF 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.ConclusionsVEGF 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.

Development of Collagen/Demineralized Bone Powder Scaffolds and Periosteum-Derived Cells for Bone Tissue Engineering Application

The aim of this study was to investigate physical and biological properties of collagen (COL) and demineralized bone powder (DBP) scaffolds for bone tissue engineering. DBP was prepared and divided into three groups, based on various particle sizes: 75–125 μm, 125–250 μm, and 250–500 μm. DBP was homogeneously mixed with type I collagen and three-dimensional scaffolds were constructed, applying chemical crosslinking and lyophilization. Upon culture with human periosteum-derived cells (PD cells), osteogenic differentiation of PD cells was investigated using alkaline phosphatase (ALP) activity and calcium assay kits. The physical properties of the COL/DBP scaffolds were obviously different from COL scaffolds, irrespective of the size of DBP. In addition, PD cells cultured with COL scaffolds showed significantly higher cell adhesion and proliferation than those with COL/DBP scaffolds. In contrast, COL/DBP scaffolds exhibited greater osteoinductive potential than COL scaffolds. The PD cells with COL/DBP scaffolds possessed higher ALP activity than those with COL scaffolds. PD cells cultured with COL/DBP scaffolds with 250–500 μm particle size yielded the maximum calcium deposition. In conclusion, PD cells cultured on the scaffolds could exhibit osteoinductive potential. The composite scaffold of COL/DBP with 250–500 μm particle size could be considered a potential bone tissue engineering implant.

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

PurposeThe 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.MethodsThirty-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.ResultsPECAM-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).ConclusionsAngiogenic 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.

Soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid is inversely associated with disease severity of knee osteoarthritis.

OBJECTIVES The aim of this study was to measure soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid of knee osteoarthritis (OA) patients and to determine the correlation between sRAGE levels and disease severity. DESIGN AND METHODS Thirty-six OA patients and 15 healthy controls were enrolled in this study. OA grading was performed using the Kellgren-Lawrence classification. sRAGE levels in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. RESULTS Plasma sRAGE levels were significantly lower in OA patients than in healthy controls (P=0.01). sRAGE levels in plasma were remarkably higher with regard to paired synovial fluid (P=0.001). Additionally, sRAGE concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity (r=-0.65, P<0.001 and r=-0.55, P=0.001, respectively). Further analysis showed that there was a strong positive correlation between plasma and synovial sRAGE concentration (r=0.81, P<0.001). CONCLUSIONS sRAGE levels were significantly lower in OA patients compared with controls, and sRAGE levels in plasma and synovial fluid also decreased significantly as the disease severity increased. Accordingly, sRAGE levels could be used as a biochemical marker for assessing the severity and progression of knee OA.