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Published in: Inflammation Research 12/2009

01-12-2009 | Original Research Paper

Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes

Authors: M. Mathy-Hartert, I. Jacquemond-Collet, F. Priem, C. Sanchez, C. Lambert, Y. Henrotin

Published in: Inflammation Research | Issue 12/2009

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Abstract

Objective and design

This study aims to investigate the effects of curcumin (Cur) on the extracellular matrix protein metabolism of articular chondrocytes and on their production of inflammatory mediators.

Methods

Human chondrocytes in alginate beads and human cartilage explants were cultured in the absence or in the presence of interleukin (IL)-1beta (10−11 M) and with or without Cur (5–20 μM). Nitric oxide (NO) synthesis was measured by the Griess spectrophotometric method; prostaglandin (PG) E2 by a specific radioimmunoassay; and IL-6, IL-8, aggrecan (Agg), matrix metalloproteinase (MMP)-3, and tissue inhibitor of metalloproteinase (TIMP)-1 by specific enzyme-amplified immunoassays. Proteoglycan degradation was evaluated by the release of 35S-glycosaminoglycans (GAG) from human cartilage explants.

Results

In alginate beads and cartilage explant models, Cur inhibited the basal and the IL-1beta-stimulated NO, PGE2, IL-6, IL-8, and MMP-3 production by human chondrocytes in a concentration-dependent manner. The TIMP-1 and the Agg productions were not modified. In the basal condition, 35S-GAG release from cartilage explants was decreased by Cur.

Conclusions

Curcumin was a potent inhibitor of the production of inflammatory and catabolic mediators by chondrocytes, suggesting that this natural compound could be efficient in the treatment of osteoarthritis.
Literature
1.
go back to reference Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil. 2008;16:137–62.CrossRefPubMed Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil. 2008;16:137–62.CrossRefPubMed
2.
go back to reference Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75:787–809.CrossRefPubMed Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75:787–809.CrossRefPubMed
3.
go back to reference Jagetia GC, Aggarwal BB. “Spicing up” of the immune system by curcumin. J Clin Immunol. 2007;27:19–35.CrossRefPubMed Jagetia GC, Aggarwal BB. “Spicing up” of the immune system by curcumin. J Clin Immunol. 2007;27:19–35.CrossRefPubMed
4.
go back to reference Li WQ, Dehnade F, Zafarullah M. Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol. 2001;166:3491–8.PubMed Li WQ, Dehnade F, Zafarullah M. Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol. 2001;166:3491–8.PubMed
5.
go back to reference Schulze-Tanzil G, Mobasheri A, Sendzik J, John T, Shakibaei M. Effects of curcumin (diferuloylmethane) on nuclear factor kappaB signaling in interleukin-1beta-stimulated chondrocytes. Ann N Y Acad Sci. 2004;1030:578–86.CrossRefPubMed Schulze-Tanzil G, Mobasheri A, Sendzik J, John T, Shakibaei M. Effects of curcumin (diferuloylmethane) on nuclear factor kappaB signaling in interleukin-1beta-stimulated chondrocytes. Ann N Y Acad Sci. 2004;1030:578–86.CrossRefPubMed
6.
go back to reference Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007;73:1434–45.CrossRefPubMed Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A. Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007;73:1434–45.CrossRefPubMed
7.
go back to reference Jackson JK, Higo T, Hunter WL, Burt HM. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res. 2006;55:168–75.CrossRefPubMed Jackson JK, Higo T, Hunter WL, Burt HM. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res. 2006;55:168–75.CrossRefPubMed
8.
go back to reference Liacini A, Sylvester J, Li WQ, Huang W, Dehnade F, Ahmad M, et al. Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes. Exp Cell Res. 2003;288:208–17.CrossRefPubMed Liacini A, Sylvester J, Li WQ, Huang W, Dehnade F, Ahmad M, et al. Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes. Exp Cell Res. 2003;288:208–17.CrossRefPubMed
9.
go back to reference Liacini A, Sylvester J, Li WQ, Zafarullah M. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol. 2002;21:251–62.CrossRefPubMed Liacini A, Sylvester J, Li WQ, Zafarullah M. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol. 2002;21:251–62.CrossRefPubMed
10.
go back to reference Shakibaei M, Schulze-Tanzil G, John T, Mobasheri A. Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study. Ann Anat. 2005;187:487–97.CrossRefPubMed Shakibaei M, Schulze-Tanzil G, John T, Mobasheri A. Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: an immunomorphological study. Ann Anat. 2005;187:487–97.CrossRefPubMed
11.
go back to reference Chowdhury TT, Salter DM, Bader DL, Lee DA. Signal transduction pathways involving p38 MAPK, JNK, NFkappaB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression. Inflamm Res. 2008;57:306–13.CrossRefPubMed Chowdhury TT, Salter DM, Bader DL, Lee DA. Signal transduction pathways involving p38 MAPK, JNK, NFkappaB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression. Inflamm Res. 2008;57:306–13.CrossRefPubMed
12.
go back to reference Toegel S, Wu SQ, Piana C, Unger FM, Wirth M, Goldring MB, et al. Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1beta-stimulated C-28/I2 chondrocytes. Osteoarthr Cartil. 2008;16:1205–12.CrossRefPubMed Toegel S, Wu SQ, Piana C, Unger FM, Wirth M, Goldring MB, et al. Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1beta-stimulated C-28/I2 chondrocytes. Osteoarthr Cartil. 2008;16:1205–12.CrossRefPubMed
13.
go back to reference Sanchez C, Mateus MM, Defresne MP, Crielaard JMR, Reginster JYL, Henrotin YE. Metabolism of human articular chondrocytes cultured in alginate beads. Longterm effects of interleukin 1 beta and nonsteroidal antiinflammatory drugs. J Rheumatol. 2002;29:772–82.PubMed Sanchez C, Mateus MM, Defresne MP, Crielaard JMR, Reginster JYL, Henrotin YE. Metabolism of human articular chondrocytes cultured in alginate beads. Longterm effects of interleukin 1 beta and nonsteroidal antiinflammatory drugs. J Rheumatol. 2002;29:772–82.PubMed
14.
go back to reference Henrotin Y, Labasse A, Zheng SX, Galais P, Tsouderos Y, Crielaard JM, et al. Strontium ranelate increases cartilage matrix formation. J Bone Miner Res. 2001;16:299–308.CrossRefPubMed Henrotin Y, Labasse A, Zheng SX, Galais P, Tsouderos Y, Crielaard JM, et al. Strontium ranelate increases cartilage matrix formation. J Bone Miner Res. 2001;16:299–308.CrossRefPubMed
15.
go back to reference Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988;115:61–9.CrossRefPubMed Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988;115:61–9.CrossRefPubMed
16.
go back to reference Labarca C, Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980;102:344–52.CrossRefPubMed Labarca C, Paigen K. A simple, rapid, and sensitive DNA assay procedure. Anal Biochem. 1980;102:344–52.CrossRefPubMed
17.
go back to reference Serteyn D, Deby-Dupont G, Pincemail J, Mottart E, Philippart C, Lamy M. Equine postanaesthetic myositis: thromboxanes, prostacyclin and prostaglandin E2 production. Vet Res Commun. 1988;12:219–26.CrossRefPubMed Serteyn D, Deby-Dupont G, Pincemail J, Mottart E, Philippart C, Lamy M. Equine postanaesthetic myositis: thromboxanes, prostacyclin and prostaglandin E2 production. Vet Res Commun. 1988;12:219–26.CrossRefPubMed
18.
go back to reference Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem. 1982;126:131–8.CrossRefPubMed Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem. 1982;126:131–8.CrossRefPubMed
19.
go back to reference Guo JF, Jourdian GW, MacCallum DK. Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res. 1989;19:277–97.CrossRefPubMed Guo JF, Jourdian GW, MacCallum DK. Culture and growth characteristics of chondrocytes encapsulated in alginate beads. Connect Tissue Res. 1989;19:277–97.CrossRefPubMed
20.
go back to reference Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Ind J Med Res. 1980;71:632–4. Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Ind J Med Res. 1980;71:632–4.
21.
go back to reference Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun. 1995;206:533–40.CrossRefPubMed Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun. 1995;206:533–40.CrossRefPubMed
22.
go back to reference Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G321–7.PubMed Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G321–7.PubMed
23.
go back to reference Laufer S. Role of eicosanoids in structural degradation in osteoarthritis. Curr Opin Rheumatol. 2003;15:623–7.CrossRefPubMed Laufer S. Role of eicosanoids in structural degradation in osteoarthritis. Curr Opin Rheumatol. 2003;15:623–7.CrossRefPubMed
24.
go back to reference Attur M, Al-Mussawir HE, Patel J, Kitay A, Dave M, Palmer G, et al. Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor. J Immunol. 2008;181:5082–8.PubMed Attur M, Al-Mussawir HE, Patel J, Kitay A, Dave M, Palmer G, et al. Prostaglandin E2 exerts catabolic effects in osteoarthritis cartilage: evidence for signaling via the EP4 receptor. J Immunol. 2008;181:5082–8.PubMed
25.
go back to reference Henrotin Y, Kurz B. Antioxidant to treat osteoarthritis: dream or reality? Curr Drug Targets. 2007;8:347–57.CrossRefPubMed Henrotin Y, Kurz B. Antioxidant to treat osteoarthritis: dream or reality? Curr Drug Targets. 2007;8:347–57.CrossRefPubMed
26.
go back to reference Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthr Cartil. 2005;13:643–54.CrossRefPubMed Henrotin Y, Kurz B, Aigner T. Oxygen and reactive oxygen species in cartilage degradation: friends or foes? Osteoarthr Cartil. 2005;13:643–54.CrossRefPubMed
27.
go back to reference Kaneko S, Satoh T, Chiba J, Ju C, Inoue K, Kagawa J. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther. 2000;6:71–9.CrossRefPubMed Kaneko S, Satoh T, Chiba J, Ju C, Inoue K, Kagawa J. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther. 2000;6:71–9.CrossRefPubMed
28.
go back to reference Flannery CR, Little CB, Hughes CE, Curtis CL, Caterson B, Jones SA. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix Biol. 2000;19:549–53.CrossRefPubMed Flannery CR, Little CB, Hughes CE, Curtis CL, Caterson B, Jones SA. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix Biol. 2000;19:549–53.CrossRefPubMed
29.
go back to reference Rowan AD, Koshy PJ, Shingleton WD, Degnan BA, Heath JK, Vernallis AB, et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 2001;44:1620–32.CrossRefPubMed Rowan AD, Koshy PJ, Shingleton WD, Degnan BA, Heath JK, Vernallis AB, et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 2001;44:1620–32.CrossRefPubMed
30.
go back to reference de Hooge AS, van De Loo FA, Arntz OJ, van Den Berg WB. Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. Am J Pathol. 2000;157:2081–91.PubMed de Hooge AS, van De Loo FA, Arntz OJ, van Den Berg WB. Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis. Am J Pathol. 2000;157:2081–91.PubMed
31.
go back to reference Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 2006;54:158–68.CrossRefPubMed Wong PK, Quinn JM, Sims NA, van Nieuwenhuijze A, Campbell IK, Wicks IP. Interleukin-6 modulates production of T lymphocyte-derived cytokines in antigen-induced arthritis and drives inflammation-induced osteoclastogenesis. Arthritis Rheum. 2006;54:158–68.CrossRefPubMed
32.
go back to reference Matsukawa A, Yoshimura T, Maeda T, Ohkawara S, Takagi K, Yoshinaga M. Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol. 1995;154:5418–25.PubMed Matsukawa A, Yoshimura T, Maeda T, Ohkawara S, Takagi K, Yoshinaga M. Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol. 1995;154:5418–25.PubMed
33.
go back to reference Woessner JF Jr, Gunja-Smith Z. Role of metalloproteinases in human osteoarthritis. J Rheumatol Suppl. 1991;27:99–101.PubMed Woessner JF Jr, Gunja-Smith Z. Role of metalloproteinases in human osteoarthritis. J Rheumatol Suppl. 1991;27:99–101.PubMed
34.
go back to reference Pelletier JP, Mineau F, Faure MP, Martel-Pelletier J. Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. Arthritis Rheumatism. 1990;33:1466–76.CrossRefPubMed Pelletier JP, Mineau F, Faure MP, Martel-Pelletier J. Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. Arthritis Rheumatism. 1990;33:1466–76.CrossRefPubMed
35.
go back to reference Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, et al. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. J Nat Prod. 2006;69:351–5.CrossRefPubMed Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, et al. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. J Nat Prod. 2006;69:351–5.CrossRefPubMed
36.
37.
go back to reference Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–900.PubMed Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–900.PubMed
38.
go back to reference Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002;11:105–11.PubMed Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002;11:105–11.PubMed
39.
go back to reference Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001;61:1058–64.PubMed Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, et al. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001;61:1058–64.PubMed
40.
go back to reference Pan MH, Lin-Shiau SY, Lin JK. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of I kappa B kinase and NF kappa B activation in macrophages. Biochem Pharmacol. 2000;60:1665–76.CrossRefPubMed Pan MH, Lin-Shiau SY, Lin JK. Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of I kappa B kinase and NF kappa B activation in macrophages. Biochem Pharmacol. 2000;60:1665–76.CrossRefPubMed
Metadata
Title
Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes
Authors
M. Mathy-Hartert
I. Jacquemond-Collet
F. Priem
C. Sanchez
C. Lambert
Y. Henrotin
Publication date
01-12-2009
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 12/2009
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-009-0063-1

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