The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave, Mandar; Attur, Mukundan; Palmer, Glyn D.; Al-Mussawir, H.; Kennish, Lauren; Patel, Jyoti; Abramson, Steven B.

doi:10.1002/art.23799

Cited by 122 publications

(108 citation statements)

References 48 publications

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“…Moreover, resveratrol was defensive to the IL-1b-induced catabolic effects of chondrocytes by elevating proteoglycan synthesis, suppressing COX-2 expression and enzyme activity, and decreasing production of MMPs 1, 3, and 13 [18]. A vivo study demonstrated that intraarticular injections of resveratrol reduced the severity of cartilage lesions by histologic examination in the experimental OA model [19].…”

Section: Discussionmentioning

confidence: 93%

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit

et al. 2011

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To observe the effect of resveratol on cartilage, chondrocyte apoptosis, and nitric oxide in experimental osteoarthritis (OA) of rabbit and to study the mechanism of resveratol in the treatment of osteoarthritis. Thirty New Zealand rabbits were randomly divided into 5 groups: group A (normal control group), group B (model control group), group C (resveratrol intervention high-dosage group), group D (resveratrol intervention middle dosage group), and group E (resveratrol intervention low-dosage group). The model of OA of the knee was established using Hulth technique in groups B, C, D, and E. After 4 weeks, group A and group B rabbits were administered daily a knees injection of dimethylsulfoxide (DMSO), whereas groups C, D, and E were administered daily a knees injection of resveratrol in DMSO in different dosages for 2 weeks. Daily dosage for rabbits of groups C, D, and E was fixed at 50, 20, and 10 μmol/kg, respectively. Then, the rabbits were killed, and the lateral cartilage sections of right femoral medial condyle were evaluated using a histological scoring system (H&E and safranin-O staining) and analyzed by TUNEL for apoptosis. Nitric oxide (NO) in synovial fluid was measured by nitrate reduction method. Histological evaluation of cartilage tissue revealed a significantly reduced cartilage destruction; the evaluation also revealed the loss of matrix proteoglycan content in cartilage in resveratrol intervention groups compared to the model control. Resveratrol reduced the apoptosis rate of chondrocyte and level of NO in the synovial fluid. In the above experiments of OA rabbits, the protective effects of resveratrol were enhanced with increased resveratrol dosage. Resveratrol controls the progression of experimental OA. One of the mechanism(s) responsible for this effect would include lowering of the apoptosis rate of chondrocyte and reducing the production of NO in experimental OA.

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Section: Discussionmentioning

confidence: 93%

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit

et al. 2011

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“…These results revealed that S1P protects cartilage degradation from inflammatory cytokineinduced GAG degradation via S1P 1 receptor activation. PGE 2 , which originates from the activation of the COX pathways, is produced by OA chondrocytes and may promote matrix degeneration (19,20). In ex vivo cultures of cartilage explants, the production of PGE 2 was increased by the stimulation of IL-1β in the supernatants of the conditioned media (Fig.…”

Section: S1p Protects Cartilage Explants From Il-1-induced Gag Lossmentioning

confidence: 99%

Sphingosine-1-phosphate inhibits interleukin-1β-induced inflammation in human articular chondrocytes

Moon

Jeong

Lee

et al. 2012

International Journal of Molecular Medicine

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Abstract. Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through a family of G-protein-coupled receptors (GPCRs) to control diverse biological processes including inflammation and woundhealing. In this study, a novel biological activity of S1P in articular chondrocytes was identified. Human primary chondrocytes were cultured in a monolayer. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were performed to detect genes and proteins involved in inflammation and cartilage degradation when human primary chondrocytes were stimulated by interleukin (IL)-1β. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by gelatin zymography. Glycosaminoglycan (GAG) degradation was evaluated using the dimethylene blue method. Prostaglandin E 2 (PGE 2 ) was measured by enzyme-linked immunosorbent assay (ELISA). By using the S1P 1 receptor agonist and antagonist, we discovered the key role played by S1P 1 in the S1P-dependent inhibition of IL-1β-induced inflammation in human chondrocytes. S1P dose-dependently inhibited IL-1β-induced NF-κB p65, cyclooxygenase (COX)-2, MMP-1, MMP-3, MMP-13 and MMP-14 mRNA expression in human chondrocytes and IL-1β-induced PGE 2 synthesis and GAG degradation in human cartilage explants. W146, a known S1P 1 receptor antagonist, inhibited the active form of NF-κB p65 and COX-2 expression induced by IL-1β. The antiinflammatory action of the S1P 1 receptor agonist SEW2871 was similar to that of S1P. This study demonstrates that S1P has anti-inflammatory effects on chondrocytes via the S1P 1 receptor. Our data suggest that targeting S1P and S1P 1 may be a potential therapy for arthritis.

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“…Resveratrol has received tremendous attention over the past couple of decades because of its benefits in several human disease models, including antioxidant effect, anti-inflammatory effect, immune regulation, and cancer chemoprevention [8][9][10]. Recent studies have shown that resveratrol also has good anti-inflammatory effects in rats with osteoarthritis [8,11]. Sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory property [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

Wang¹,

Ren²,

Chen

et al. 2015

Cell Physiol Biochem

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Objective: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. Methods: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint cavity. IL-1β, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. Results: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1β, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1β, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. Conclusion: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

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The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Cited by 122 publications

References 48 publications

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit

Sphingosine-1-phosphate inhibits interleukin-1β-induced inflammation in human articular chondrocytes

Effect of Sodium Alginate Addition to Resveratrol on Acute Gouty Arthritis

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