Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Rheumatology International (Impact Factor: 1.52). 04/2011; 32(4):985-90. DOI: 10.1007/s00296-010-1731-8
Source: PubMed


The aim of this study is to investigate visfatin levels in both synovial fluid (SF) and plasma of patients with primary knee osteoarthritis (OA) and its relationship with biomarkers of cartilage degradation in SF. Thirty OA patients, 12 SF control, and 12 plasma control subjects were enrolled in this study. Visfatin levels in both SF and plasma were measured using enzyme-linked immunosorbent assay (ELISA). Degradation biomarkers of collagen II and aggrecan in SF were also measured. The radiographic grading of OA in the knee was performed by the Kellgren-Lawrence (KL) criteria. Compared to controls, OA patients had higher SF visfatin concentration (8.95 ± 2.5 vs. 4.48 ± 2.49 ng/ml, P < 0.001). SF visfatin levels in KL grade 4 were significantly elevated compared with those of KL grade 3 (10.57 ± 2.49 vs. 7.54 ± 1.5 ng/ml, P = 0.001). SF visfatin positively correlated with degradation biomarker of collagen II, CTX-II (r = 0.497, P = 0.005), and degradation biomarker of aggrecan, AGG1 (r = 0.451, P = 0.012) and AGG2 (r = 0.434, P = 0.017). These findings suggest that SF visfatin might involved in cartilage matrix degradation.

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    • "These epigenetic changes elicit an imbalance between chondrocyte catabolism and anabolism, leading to OA development. synthesis and increases the expression of matrix-degradative enzymes (Duan et al., 2012; Gosset et al., 2008; Yammani and Loeser, 2012; Yang et al., 2015). Notably, visfatin can be localized intracellularly, serving as a regulator of salvage pathways of NAD + synthesis. "
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    • "This adipokine increases the expression of ADAMTS4, ADAMTS5, MMP-3, and MMP-13, which are very relevant cartilage degradative enzymes [136]. Moreover, OA patients had higher synovial fluid visfatin concentrations, which are correlated with degradation biomarkers such as collagen type II and aggrecan [68]. Taken together, these data indicate that visfatin develops catabolic functions at cartilage level and it could play an important role in the pathophysiology of OA. "
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    • "Similarly, other mediators such as TNFα or IL-1β are released by the action of OA-activated synovial membrane on adjacent cartilage and subchondral bone tissues [2]. In agreement with Duan and colleagues, visfatin/Nampt was present in synovial fluid from OA patients [38]. "
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    ABSTRACT: 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 OA chondrocytes and osteoblasts by studying Nampt enzymatic activity. 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. In tissular explants, conditioned media and synovial fluid, visfatin/Nampt was found as a homodimer, corresponding to the enzymatically active conformation. All human OA joint tissues released visfatin/Nampt (synovium: 628 +/- 106 ng/g tissue; subchondral bone: 195 +/- 26 ng/g tissue; cartilage: 152 +/- 46 ng/g tissue), with significantly higher level for synovium (P <0.0005). Nampt activity was identified ex vivo in synovium. In vitro, visfatin/Nampt significantly induced the expression of interleukin 6, keratinocyte chemoattractant and monocyte chemoattractant protein 1 in chondrocytes and osteoblasts. APO866 decreased the mRNA and protein levels of these pro-inflammatory cytokines in the two cell types (up to 94% and 63% inhibition, respectively). Levels of growth factors (vascular endothelial growth factor, transforming growth factor beta) and hypertrophic genes were unchanged with treatment. Visfatin/Nampt is released by all human OA tissues in a dimeric enzymatically active conformation and mostly by the synovium, which displays Nampt activity. The Nampt activity of visfatin is involved in chondrocyte and osteoblast activation, so targeting this enzymatic activity to disrupt joint tissue interactions may be novel in OA therapy.
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