Visfatin increases the activity of aggrecanases-1 and -2 in human chondrocytes (original) (raw)
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Arthritis Research & Therapy, 2014
Visfatin is an adipokine that may be involved in intertissular joint communication in osteoarthritis (OA). With a homodimeric conformation, it exerts nicotinamide phosphoribosyltransferase (Nampt) enzymatic activity, essential for nicotinamide adenine dinucleotide biosynthesis. We examined the tissular origin and conformation of visfatin/Nampt in human OA joints and investigated the role of visfatin/Nampt in chondrocytes and osteoblasts by studying Nampt enzymatic activity. Methods: Synovium, cartilage and subchondral bone from human OA joints were used for protein extraction or incubated for 24 hours in serum-free media (conditioned media), and synovial fluid was obtained from OA patients. Visfatin/Nampt expression in tissular extracts and conditioned media was evaluated by western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Nampt activity was assessed in OA synovium by colorimetric assay. Primary cultures of murine chondrocytes and osteoblasts were stimulated with visfatin/Nampt and pretreated or not with APO866, a pharmacologic inhibitor of Nampt activity. The effect on cytokines, chemokines, growth factors and hypertrophic markers expression was examined by quantitative reverse transcriptase polymerase chain reaction and/or ELISA.
European review for medical and pharmacological sciences, 2011
Expedited research on Obesity has confirmed that, adipose tissue is highly active in secreting a variety of proteins, one among them is visfatin. It was originally identified as Pre B cell Colony Enhancing Factor (PBEF), to be secreted by the lymphocytes and can act as a cytokine with immune regulatory action. Besides, it acts as Nicotinamide phosphoribosyl transferase (Nampt), an enzyme involved in the NAD+ salvage pathway. It has been shown to help in the regulation of glucose homeostasis, but whether it binds to insulin receptor and exerts insulin mimetic activity is still a controversy. Visfatin has antiapoptotic activity and has a regulatory role in inflammation. Several studies have identified changes in the circulatory levels of visfatin in diseases. Notable among them are obesity, diabetes mellitus, kidney diseases and bone disorders. It is a molecule of clinical relevance and could be a promising biomarker with diagnostic and prognostic significance.
International Journal of Molecular Sciences, 2018
Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were...
Annals of the Rheumatic Diseases, 2013
EWRR abstracts autoantibodies. We have shown increased serum levels of B-cell activating factor of the TNF family (BAFF) in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM) patients and its association with disease activity. Here we evaluated serum levels of visfatin in anti-Jo-1-positive PM/DM patients, its expression in muscle tissue and investigated potential relations between visfatin, BAFF, disease activity and anti-Jo-1 autoantibody levels. Material and Methods ELISA was used for detection of visfatin, BAFF and anti-Jo-1 serum samples in patients with PM (n = 27), DM (n = 11) and in 25 age and sex matched healthy controls. Paired samples from two different time points of sixteen patients were available. Disease activity was evaluated by myositis disease activity assessment visual analogue scales (MYOACT) and by serum levels of creatine phosphokinase (CPK), aminotranspherases (ALT, AST), lactate dehydrogenase (LDH) and myoglobin. Visfatin was detected by immunohistochemistry in muscle tissues of PM/DM patients (n = 5/5) and compared with non-inflammatory control muscle tissues from patients with myasthenia gravis (n = 5). Results Serum visfatin and BAFF levels were significantly higher in myositis patients (medians 1.9 and 1.4 pg/l) compared to healthy controls (1.3 and 1.0 pg/l; p < 0.02 and p = 0.003) and were associated with clinical muscle activity (rs = 0.39; p < 0.02 and rs = 0.34; p = 0.04). Trend for correlation of both visfatin and BAFF with the global disease activity was present. Serum levels of visfatin were associated with LDH (rs = 0.39, p < 0.02), whereas BAFF correlated with CPK, myoglobin and AST (rs = 0.51, 0.57 and 0.39; p < 0.05 for all). Positive correlation between visfatin and BAFF serum levels was found in patients with myositis (rs = 0.44; p < 0.01) but was negative in healthy controls (rs =-0.54; p < 0.001). No association between visfatin and anti-Jo-1 autoantibody levels was found while BAFF positively correlated with anti-Jo-1 levels (rs = 0.85; p = 0.001). Visfatin levels decreased significantly over time (p = 0.01), while the decrease of BAFF was not significant. Visfatin expression was present in endomysial and perimysial inflammatory infiltrates of muscle tissues from patients with PM/DM compared with no expression in controls. Conclusions These results demonstrate that serum levels of visfatin, similarly to BAFF, associate with disease activity in patients with myositis. Increased visfatin levels and expression in inflamed muscle tissues support its potential role in the pathogenesis of idiopathic inflammatory myopathies.
Arthritis Research & Therapy, 2009
Introduction The role of adiponectin in the pathogenesis of arthritis is still controversial. This study was performed to examine whether adiponectin is involved in joint inflammation and destruction in rheumatoid arthritis (RA) in relation to the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Methods Synovial cells from RA patients were treated with adiponectin or interleukin (IL)-1β for 24 hours. The culture supernatant was collected and analyzed for the levels of IL-6, IL-8, prostaglandin E 2 (PGE 2), VEGF, and MMPs by enzyme-linked immunosorbent assay. The levels of adiponectin, VEGF, MMP-1, and MMP-13 in the joint fluids from 30 RA or osteoarthritis (OA) patients were also measured. Results Adiponectin at the concentration of 10 μg/mL stimulated the production of IL-6, IL-8, and PGE 2 in RA fibroblast-like synoviocytes (FLSs), although the level of these was much lower than with 1 ng/mL IL-1β. However, adiponectin stimulated the production of VEGF, MMP-1, and MMP-13 at the same level as IL-1β. In addition, the level of adiponectin and MMP-1 in the joint fluid of RA patients was significantly higher than in OA patients. Adiponectin was positively correlated with VEGF in RA patients but not in OA patients, while the level of MMPs in joint fluid was not correlated with adiponectin in either RA or OA patients. Conclusions Adiponectin may play a significant role in the pathogenesis of RA by stimulating the production of VEGF and MMPs in FLSs, leading to joint inflammation and destruction, respectively.
Arthritis & Rheumatism, 2002
Objective. Osteoarthritic (OA) cartilage destruction depends on collagen-and aggrecan-degrading proteases such as collagenases (MMP-1 and MMP-13), stromelysin (MMP-3), MMP-14, as well as the so-called aggrecanases (ADAM-TS4 and ADAM-TS5). In this study, we tried to clarify whether these proteases are expressed in vivo in human normal and OA cartilage (and whether they are up-regulated or down-regulated during the disease process) and in interleukin-1 (IL-1)-stimulated chondrocytes in vitro. Methods. Quantitative polymerase chain reaction assays were developed and performed on RNA isolated directly from normal and degenerative cartilage tissue as well as from primary human articular chondrocytes cultured with and without IL-1. Results. In vivo, MMP-1 was detectable only at very low levels in any condition. MMP-13 expression was low in normal and early degenerative cartilage but was strongly up-regulated in late-stage OA specimens. MMP-1 and MMP-13 were expressed much higher in vitro than in vivo and were up-regulated by IL-1. Among all proteases, MMP-3 was by far the most strongly expressed, although it was strongly downregulated in late-stage OA specimens. Expression of MMP-3 was higher in vitro than in vivo and was up-regulated by IL-1. ADAM-TS5 and MMP-14 were expressed in all sample groups. Expression of ADAM-TS4 was very low in vivo and was induced in vitro after stimulation by IL-1. Conclusion. Our expression data clearly support MMP-13 as the major collagenase in OA cartilage. The most strongly expressed aggrecanase was ADAM-TS5. ADAM-TS4 was expressed only at a very low level in normal cartilage and was only slightly up-regulated in OA cartilage, casting doubt on this enzyme being the relevant aggrecanase of articular cartilage. Results of our study show that expression of many enzymes is significantly different in vitro and in vivo and suggest that IL-1 stimulation of articular chondrocytes might not be a good model for the matrix catabolism in OA cartilage.
Visfatin levels and intima-media thicknesses in rheumatic diseases
Clinical Rheumatology, 2010
Chronic inflammatory rheumatic diseases lead to increased prevalence of atherosclerosis. However, this early and accelerated atherosclerosis cannot be explained by traditional cardiovascular risk factors alone. The permanent overexpression of cellular adhesion molecules and proinflammatory cytokines in chronic inflammatory conditions may participate in accelerated atherosclerosis. Visfatin, a novel adipocytokine, has a potential insulin-like action and pro-inflammatory effects. Therefore, the aim of the study was to determine serum visfatin level and its association with common carotid intima-media thickness (IMT), which is a predictor of atherosclerosis, in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Behçet's disease (BD). The study involved 29 RA, 26 SLE, 25 SSc, 30 BD patients, and 29 healthy controls (HC). Serum levels of TNF-α, IL-6, and visfatin were analyzed using enzyme-linked immunosorbent assay method and homeostasis model assessment for insulin resistance (HOMA-IR) indexes, and IMTs were determined. Serum visfatin level was higher in the RA group than all the other groups. In addition, visfatin level was higher in the active BD subgroup than the inactive BD subgroup. In the study groups, visfatin levels were not correlated with HOMA-IR indexes and IMTs. Whereas visfatin serum concentration was not associated with insulin resistance and carotid atherosclerosis in selected rheumatic diseases, it was higher in the RA and active BD groups, but not in the SLE and SSc groups. Visfatin levels may be associated with Th1/Th2 balance. Further studies are needed for more precise elucidation of the proinflammatory activities of visfatin.