Effect of resveratrol in experimental osteoarthritis in rabbits

Elmalı, Nurzat; Esenkaya, Irfan; Harma, Ahmet; Ertem, Kadir; Türköz, Yusuf; Mizrak, Biilent

doi:10.1007/s00011-004-1341-6

Cited by 150 publications

(123 citation statements)

References 31 publications

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“…Others have reported that SIRT1 associates with Runx2 and reduces its acetylation status (40). SIRT1 activation with resveratrol promotes osteoblast differentiation in vitro (40 -43) and prevents bone loss in vivo (44). These observations are the compelling systematic biological rationale for our focus on SIRT1 in bone.…”

Section: Discussionmentioning

confidence: 93%

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Fei

Shimizu

McBurney³

et al. 2015

Journal of Biological Chemistry

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Background: Parathyroid hormone (PTH) stimulates MMP13 in osteoblasts. Results: Sirtuin 1 (SIRT1) activation suppresses PTH stimulation of Mmp13 expression, and this process is mediated by the AP-1 complex. Conclusion: SIRT1 is a novel suppressor of PTH stimulation of MMP13 expression. Significance: Activation of SIRT1 and suppression of MMP13 may prolong the anabolic bone-forming period of PTH treatment in osteoporotic patients.

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Section: Discussionmentioning

confidence: 93%

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Fei

Shimizu

McBurney³

et al. 2015

Journal of Biological Chemistry

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“…Our results indicate that resveratrol exerts salutary effects on chondrocyte metabolism by reversing IL-1␤-mediated catabolic effects on proteoglycan synthesis and apoptotic cell death. Recently, Elmali et al showed that intraarticular injections of resveratrol, starting at the onset of disease, protected cartilage against the development of experimentally induced OA in rabbits (18).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, resveratrol exerts antiinflammatory or antiproliferative effects on numerous cell types, including macrophages and neutrophils (11,12), human mammary epithelial cells (13), 3T6 fibroblasts (14), and colon cancer cells (15). In vivo, resveratrol has shown beneficial effects in animal models of carcinogenesis (7), atherosclerosis (16), and Alzheimer's disease (17) and in a rabbit model of OA (18).…”

mentioning

confidence: 99%

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

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

119

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Objective. To determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).Methods. Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1␤ (IL-1␤) stimulation were assessed by measurement of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.Results. Resveratrol inhibited both spontaneous and IL-1␤-induced PGE 2 production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB 4 production was reduced by >50% (P < 0.05). The production of PGE 2 was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1␤-induced ATP depletion. Similarly, IL-1␤-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE 2 abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.Conclusion. Resveratrol protects against IL-1␤-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE 2 synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.

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“…To evaluate the metabolic responses of pig erythrocytes compared to human ones and in the light of the acquired experiences we also tested two different drugs: GFZ and RV which are known to bind Hb [25]- [27]. GFZ belongs to the group of fibric acid derivatives, utilized as antihyperlipidemia agents with the main aim to reduce incidence of coronary heart disease [28] [29]; RV, an important phytoalexine found in many plants, has been shown to be significantly effective in the treatment of several pathological conditions such as cancer, coronary heart disease and osteoarthritis [30]- [32]. The results shown in Figure 4 highlight a different response of the pig RBCs to the two drugs that becomes more evident when compared to human RBCs.…”

Section: Resultsmentioning

confidence: 99%

Metabolic Effects of Endogenous and Exogenous Heterotropic Hemoglobin Modulators on Anion Transport: The Case of Pig Erythrocytes

Tellone

Russo²,

Giardina³

et al. 2015

OALib

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This comparative study, focused on the anion kinetic of band 3 protein of pig erythrocytes, investigates in vitro the metabolic functionality of the red blood cells of this mammal which show particular characteristics of the cell membrane and significant stoichiometric variations of several cytosolic components. Pig red blood cells compared to human ones, are characterized by a higher anion flux strongly modulated by the conformational transition state (T-R) of hemoglobin; these findings are probably connected to the intracellular concentration of 2,3-disphosphoglycerate and to chloride activity. The experimental use, alone or in combination, of some exogenous heterotropic modulators of hemoglobin as orthovanadate, gemfibrozil and resveratrol, shows characteristic modulations of the anion flux which are related to the cytosolic metabolites physiologically present in pig erythrocytes, to the metabolism and oxidative stress. Our findings highlight new features about the pig red blood cells functionality and contribute to extending the current understanding of their life cycle, providing opportunities for new investigations in the field of comparative physiology.

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Effect of resveratrol in experimental osteoarthritis in rabbits

Abstract: A characteristic parameter in arthritis is the progressive loss of articular cartilage. This study suggests that intraarticular injections of resveratrol starting at the onset of disease may protect cartilage against the development of experimentally induced OA.

Cited by 150 publications

References 31 publications

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

Sirtuin 1 Is a Negative Regulator of Parathyroid Hormone Stimulation of Matrix Metalloproteinase 13 Expression in Osteoblastic Cells

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

Metabolic Effects of Endogenous and Exogenous Heterotropic Hemoglobin Modulators on Anion Transport: The Case of Pig Erythrocytes

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