Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity

Lei, Ming; Wang, Ji-Guo; Xiao, Deming; Fan, Meng; Wang, Daping; Xiong, Jianyi; Chen, Yang; Ding, Yongsheng; Shang-li, Liu

doi:10.1016/j.ejphar.2011.10.015

Cited by 106 publications

(80 citation statements)

References 39 publications

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“…The similar result was found by Huang et al, 2004, where they demonstrated that emodin, an active component of rhizome of Rheum palmatum, suppressed 12-O-tetradecanoylphorbol-13-acetate-mediated IkB-α degradation and p65 nuclear translocation in human skin squamous cell carcinoma (HSC5) and breast cancer cell line (MDA-MB-231). A recent study also indicated that resveratrol inhibited lipopolysaccharide (LPS)-stimulated nuclear translocation of p65-NF-κB in endothelial cells (Lei et al, 2012). The results of the present study are also highly consistent with those of an earlier study performed in human dermal fibroblast cells; in that study, it was found that Astragalus membranaceus, a tonic in traditional Korean medicine, inhibits MMP-1 expression by suppressing p65-NF-κB translocation (Hong et al, 2012).…”

Section: Discussionsupporting

confidence: 94%

Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation

Huang

Chang

et al. 2015

European Journal of Pharmacology

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Section: Discussionsupporting

confidence: 94%

Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation

Huang

Chang

et al. 2015

European Journal of Pharmacology

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“…The protein extracts were then electrophoretically resolved by SDS-PAGE (10-20 mg protein/lane) and transferred onto PVDF membranes for immunoblot analysis. The blots were processed (19)(20)(21) and then probed with the indicated antibodies. The after antibodies were used for b-actin (47778; Santa Cruz Biotechnology, TX, USA), a2tubulin (T5168; Sigma-Aldrich), SIRT1 (07-131; EMD-Millipore), Ac-H3K9/14 (A-4021-050; EMDMillipore), 2MeH3K9 (07441; EMD-Millipore), MMP13 (sc-81547; Santa Cruz Biotechnology), LEF1 (2230; Cell Signaling Technology ), and b-catenin (ab16051; Abcam, Cambridge, United Kingdom).…”

Section: Protein and Immunoblot Analysesmentioning

confidence: 99%

“…Correspondingly, additional in vivo studies (14) demonstrated that Sirt1 exerts an anti-inflammatory effect in cartilage during OA. Moreover, mechanistic studies have provided further support that SIRT1 promotes chondrocyte survival through various pathways (15)(16)(17)(18)(19)-in particular, deacetylation of p65/ RelA-which reduces iNOS gene expression after IL-1b challenge of chondrocytes (20). Despite the wealth of information regarding the beneficial effects exerted by SIRT1 in maintaining chondrocyte survival and attenuating inflammation, very little is known about the impact of SIRT1 on cartilage destruction during OA.…”

mentioning

confidence: 99%

LEF1‐mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes

et al. 2017

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Reduced SIRT1 activity and levels during osteoarthritis (OA) promote gradual loss of cartilage. Loss of cartilage matrix is accompanied by an increase in matrix metalloproteinase (MMP) 13, partially because of enhanced LEF1 transcriptional activity. In this study, we assessed the role of SIRT1 in LEF1-mediated MMP13 gene expression in human OA chondrocytes. Results showed that MMP13 protein levels and enzymatic activity decreased significantly during SIRT1 overexpression or activation by resveratrol. Conversely, MMP13 gene expression was reduced in chondrocytes transfected with SIRT1 siRNA or treated with nicotinamide (NAM), a sirtuin inhibitor. Chondrocytes challenged with IL-1b, a cytokine involved in OA pathogenesis, enhanced LEF1 protein levels and gene expression, resulting in increased MMP13 gene expression; however, overexpression of SIRT1 during IL-1b challenge impeded LEF1 levels and MMP13 gene expression. Previous reports showed that LEF1 binds to the MMP13 promoter and transactivates its expression, but we observed that SIRT1 repressed LEF1 protein and mRNA expression, ultimately reducing LEF1 transcriptional activity, as judged by luciferase assay. Finally, mouse articular cartilage from Sirt1 2/2 presented increased LEF1 and MMP13 protein levels, similar to human OA cartilage. Thus, demonstrating for the first time that SIRT1 represses MMP13 in human OA chondrocytes, which appears to be mediated, at least in part, through repression of the transcription factor LEF1, a known modulator of MMP13 gene expression.-Elayyan, J., Lee, E.-J., Gabay, O., Smith, C. A., Qiq, O., Reich, E., Mobasheri, A., Henrotin, Y., Kimber, S. J., Dvir-Ginzberg, M. LEF1-mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes. FASEB J. 31, 3116-3125 (2017). www.fasebj.orgArticular cartilage undergoes age-related degenerative changes leading to the joint disease osteoarthritis (OA). Gradual loss of hyaline joint cartilage during OA is evoked through chronic synovitis, which involves the accumulation of proinflammatory cytokines, as IL1b, TNF-a, and IL6 within the joint (1-5), subsequently leading to a steady increase in matrix metalloproteinases (MMPs) and a disintegrin and MMP with thrombospondin motifs (ADAMTS) proteins, which further promote cartilage destruction (6-12). Recent experimental attempts ABBREVIATIONS: ACAN, aggrecan gene; ADAMTS, a disintegrin and metalloproteinase with thrombospondin-like motifs; BMP, bone morphogenic protein; ChIP, chromatin immunoprecipitation; COL2A1, collagen-2 a-1 gene; FBS, fetal bovine serum; FGF, fibroblast growth factor; GDF, growth differentiation factor; GSK3b, glycogen synthase kinase-3b; hESC, human embryonic stem cell; KO, knockout; LEF, lymphoid enhancer factor; MMP, matrix metalloproteinase; NAM, nicotinamide adenine mononucleotide; OA, osteoarthritis; Res, resveratrol; qPCR, quantitative PCR; siRNA, small interfering RNA; SIRT1, silent mating type information regulation 2 homolog 1 (sirtuin-1); SOX9, sex-determining-region-on-the-Y-chromosome-relate...

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“…Resveratrol decreases OA score when directly injected intraarticularly in the rabbit anterior cruciate ligament transection model of OA (122,123) . It is an NF-κB inhibitor in chondrocytes and blocks inflammation and apoptosis (124)(125)(126) . It has also been shown to decrease proteolysis (e.g.…”

Section: Resveratrolmentioning

confidence: 99%

The potential for dietary factors to prevent or treat osteoarthritis

et al. 2014

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Osteoarthritis (OA) is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Increasing age and obesity are both major risk factors for OA and the health and economic burden of this disease will increase in the future. Focusing on compounds from the habitual diet that may prevent the onset or slow the progression of OA is a strategy that has been under-investigated to date. An approach that relies on dietary modification is clearly attractive in terms of risk/benefit and more likely to be implementable at the population level. However, before undertaking a full clinical trial to examine potential efficacy, detailed molecular studies are required in order to optimise the design. This review focuses on potential dietary factors that may reduce the risk or progression of OA, including micronutrients, fatty acids, flavonoids and other phytochemicals. It therefore ignores data coming from classical inflammatory arthritides and nutraceuticals such as glucosamine and chondroitin. In conclusion, diet offers a route by which the health of the joint can be protected and OA incidence or progression decreased. In a chronic disease, with risk factors increasing in the population and with no pharmaceutical cure, an understanding of this will be crucial.Osteoarthritis: Diet: Cartilage: Bioactive: Polyphenol: Phytochemical: Flavonoid Osteoarthritis (OA) is a degenerative joint disease characterised by degradation of articular cartilage, thickening of subchondral bone and osteophyte formation. Incidence and prevalence of OA has been difficult to assess, in part because of heterogeneity in definitions of the disease. A recent meta-analysis suggested that overall prevalence of OA at different anatomical sites was 23·9 % (knee), 10·9 % (hip) and 43·3 % (hand), although only the prevalence of knee OA showed a gender difference between women and men (27·3 and 21 %, respectively)(1) . Osteoarthritis is a leading cause of disability in the UK. A recent survey (2) found 8·5 million people in the UK with OA, with 71 % of these in constant pain. There are no effective disease-modifying drugs to treat OA and drugs that relieve pain are often insufficient. Joint replacement is offered to patients at end-stage disease with 66 436 hip and 77 578 knee replacements due to OA performed in the UK in 2011 (3) . Two major risk factors for OA are increasing age (most affected patients are aged >45 years and the greatest morbidity is seen in patients aged >60 years) (4) and increasing obesity (5) . With changing demographics, OA is an increasing public health and economic burden. The economic costs of OA in the UK are largely unknown, but direct costs have been estimated at approximately £1 billion/year. With inclusion of indirect costs, estimates from the USA range up to £8 billion/ year (6) .*Corresponding author: I. M. Clark, fax 01603-592250, email i.clark@uea.ac.uk †These authors contributed equally to this review.Abbreviations: ADAMTS, a disintegrin and metalloproteina...

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Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity

Cited by 106 publications

References 39 publications

Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation

Hinokitiol, a tropolone derivative, inhibits mouse melanoma (B16-F10) cell migration and in vivo tumor formation

LEF1‐mediated MMP13 gene expression is repressed by SIRT1 in human chondrocytes

The potential for dietary factors to prevent or treat osteoarthritis

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