{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:17:16Z","timestamp":1790824636000,"version":"4.1.0"},"update-to":[{"DOI":"10.12688\/f1000research.2-147.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T00:00:00Z","timestamp":1376956800000}}],"reference-count":52,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T00:00:00Z","timestamp":1376956800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Objective:<\/ns4:bold>\n                    <ns4:italic\/>\n                    Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1\u03b2)-stimulated inflammation and catabolism in an explant model of cartilage inflammation.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    <ns4:italic\/>\n                    Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3\u03bcM-100\u03bcM. Prostaglandin E\n                    <ns4:sub>2<\/ns4:sub>\n                    (PGE\n                    <ns4:sub>2<\/ns4:sub>\n                    ) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1\u03b2-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live\/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    <ns4:italic\/>\n                    Curcumin induced chondrocyte death in primary cultures (50\u03bcM p&lt;0.001\u00a0and 100\u03bcM\n                    <ns4:italic>p&lt;<\/ns4:italic>\n                    0.001) after 24 hours. After 48 hours and five days, curcumin (\u226525\u03bcM) significantly increased cell death (\n                    <ns4:italic>p&lt;<\/ns4:italic>\n                    0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25\u03bcM after five days. Curcumin (\u22653\u03bcM) significantly reduced IL-1\u03b2-stimulated PG (\n                    <ns4:italic>p<\/ns4:italic>\n                    &lt;0.05) and PGE\n                    <ns4:sub>2<\/ns4:sub>\n                    release (\n                    <ns4:italic>p&lt;<\/ns4:italic>\n                    0.001) from explants, whilst curcumin (\u226512\u03bcM) significantly reduced MMP-3 release (\n                    <ns4:italic>p&lt;<\/ns4:italic>\n                    0.01).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusion:<\/ns4:bold>\n                    Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.\n                  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Maiotti","year":"2000","journal-title":"Arthroscopy."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"301-308","DOI":"10.1093\/ecam\/neh117","article-title":"Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review.","volume":"2","author":"S Ahmed","year":"2005","journal-title":"Evid Based Complement Alternat Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1-6","DOI":"10.1007\/s10753-006-9012-0","article-title":"Effects of resveratrol in inflammatory arthritis.","volume":"30","author":"N Elmali","year":"2007","journal-title":"Inflammation."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"163-172","DOI":"10.1016\/S0027-5107(02)00332-9","article-title":"Mechanism-based in vitro screening of potential cancer chemopreventive agents.","volume":"523\u2013524","author":"C Gerhauser","year":"2003","journal-title":"Mutat Res."},{"key":"ref-5","doi-asserted-by":"crossref","first-page":"3474-3483","DOI":"10.4049\/jimmunol.163.6.3474","article-title":"Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity.","volume":"163","author":"C Jobin","year":"1999","journal-title":"J Immunol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"1434-1445","DOI":"10.1016\/j.bcp.2007.01.005","article-title":"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.","volume":"73","author":"M Shakibaei","year":"2007","journal-title":"Biochem Pharmacol."},{"key":"ref-7","first-page":"43","article-title":"Toxic effects of curcumin (diferuloylmethane) on equine articular chondrocytes and synoviocytes in vitro.","volume":"16","author":"A Clutterbuck","year":"2008","journal-title":"Eur Cell Mater."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1205-1212","DOI":"10.1016\/j.joca.2008.01.013","article-title":"Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1beta-stimulated C-28\/I2 chondrocytes.","volume":"16","author":"S Toegel","year":"2008","journal-title":"Osteoarthritis Cartilage."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"3395-3403","DOI":"10.1002\/art.11341","article-title":"Molecular phenotyping of human chondrocyte cell lines T\/C-28a2, T\/C-28a4, and C-28\/I2.","volume":"48","author":"F Finger","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1363-1369","DOI":"10.2460\/ajvr.2002.63.1363","article-title":"Effects of carprofen and dexamethasone on canine chondrocytes in a three-dimensional culture model of osteoarthritis.","volume":"63","author":"L Dvorak","year":"2002","journal-title":"Am J Vet Res."},{"key":"ref-11","first-page":"75-85","article-title":"Chondrocyte apoptosis induced by nitric oxide.","volume":"146","author":"F Blanco","year":"1995","journal-title":"Am J Pathol."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"247-248","DOI":"10.3109\/03008208209160269","article-title":"A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures.","volume":"9","author":"R Farndale","year":"1982","journal-title":"Connect Tissue Res."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/2193-1801-2-56","article-title":"Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management.","volume":"2","author":"Y Henrotin","year":"2013","journal-title":"Springerplus."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"4202-4232","DOI":"10.3390\/ijms13044202","article-title":"Scientific evidence and rationale for the development of curcumin and resveratrol as nutraceutricals for joint health.","volume":"13","author":"A Mobasheri","year":"2012","journal-title":"Int J Mol Sci."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"141-149","DOI":"10.1016\/j.joca.2009.10.002","article-title":"Biological actions of curcumin on articular chondrocytes.","volume":"18","author":"Y Henrotin","year":"2010","journal-title":"Osteoarthritis Cartilage."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"788-795","DOI":"10.1124\/jpet.105.084434","article-title":"Curcumin suppresses interleukin 1beta-mediated microsomal prostaglandin E synthase 1 by altering early growth response gene 1 and other signaling pathways.","volume":"315","author":"Y Moon","year":"2005","journal-title":"J Pharmacol Exp Ther."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"1199-1208","DOI":"10.1093\/carcin\/bgg082","article-title":"Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt.","volume":"24","author":"J Woo","year":"2003","journal-title":"Carcinogenesis."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"R165","DOI":"10.1186\/ar2850","article-title":"Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.","volume":"11","author":"C Csaki","year":"2009","journal-title":"Arthritis Res Ther."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"317-325","DOI":"10.1006\/abbi.1996.0397","article-title":"Contributions of fluid convection and electrical migration to transport in cartilage: relevance to loading.","volume":"333","author":"A Garcia","year":"1996","journal-title":"Arch Biochem Biophys."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"343-355","DOI":"10.1016\/S0945-053X(99)00027-X","article-title":"beta-Integrin-collagen interaction reduces chondrocyte apoptosis.","volume":"18","author":"L Cao","year":"1999","journal-title":"Matrix Biol."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"693-699","DOI":"10.1016\/j.arthro.2006.05.006","article-title":"In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes.","volume":"22","author":"C Chu","year":"2006","journal-title":"Arthroscopy."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"1076-1085","DOI":"10.1002\/art.23381","article-title":"The effect of glycosaminoglycan loss on chondrocyte viability: a study on porcine cartilage explants.","volume":"58","author":"S Otsuki","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"254-261","DOI":"10.1006\/cyto.2001.1001","article-title":"Mechanism of inhibition of endothelin-1-stimulated proteoglycan and collagen synthesis in rat articular chondrocytes.","volume":"17","author":"A Khatib","year":"2002","journal-title":"Cytokine."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"319-325","DOI":"10.1006\/excr.1995.1161","article-title":"IL-1-induced nitric oxide inhibits chondrocyte proliferation via PGE2.","volume":"218","author":"F Blanco","year":"1995","journal-title":"Exp Cell Res."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"15-21","DOI":"10.1006\/bbrc.1995.1003","article-title":"Nitric oxide activates metalloprotease enzymes in articular cartilage.","volume":"206","author":"G Murrell","year":"1995","journal-title":"Biochem Biophys Res Commun."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"533-540","DOI":"10.1006\/bbrc.1995.1076","article-title":"Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages.","volume":"206","author":"I Brouet","year":"1995","journal-title":"Biochem Biophys Res Commun."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"428-435","DOI":"10.1111\/j.1749-6632.2009.04687.x","article-title":"Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.","volume":"1171","author":"A Clutterbuck","year":"2009","journal-title":"Ann N Y Acad Sci."},{"key":"ref-28","first-page":"89-91","article-title":"Production of cytokines by chondrocytes and its role in proteoglycan degradation.","volume":"27","author":"M Shinmei","year":"1991","journal-title":"J Rheumatol Suppl."},{"key":"ref-29","first-page":"232-240","article-title":"Chondrocyte matrix metalloproteinase-8: up-regulation of neutrophil collagenase by interleukin-1 beta in human cartilage from knee and ankle joints.","volume":"74","author":"S Chubinskaya","year":"1996","journal-title":"Lab Invest."},{"key":"ref-30","first-page":"680-690","article-title":"Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.","volume":"66","author":"Y Okada","year":"1992","journal-title":"Lab Invest."},{"key":"ref-31","first-page":"19-25","article-title":"Recombinant equine interleukin-1beta induces putative mediators of articular cartilage degradation in equine chondrocytes.","volume":"66","author":"J Tung","year":"2002","journal-title":"Can J Vet Res."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"516-525","DOI":"10.1002\/art.20004","article-title":"Inhibition of interleukin-1beta-stimulated production of matrix metalloproteinases by hyaluronan via CD44 in human articular cartilage.","volume":"50","author":"S Julovi","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"477-496","DOI":"10.1111\/j.1440-1827.2010.02547.x","article-title":"Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases.","volume":"60","author":"T Shiomi","year":"2010","journal-title":"Pathol Int."},{"key":"ref-34","doi-asserted-by":"crossref","first-page":"15579-15582","DOI":"10.1016\/S0021-9258(18)98442-5","article-title":"Cleavage of cartilage proteoglycan between G1 and G2 domains by stromelysins.","volume":"266","author":"A Fosang","year":"1991","journal-title":"J Biol Chem."},{"key":"ref-35","doi-asserted-by":"crossref","first-page":"273-276","DOI":"10.1042\/bj2950273","article-title":"Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain.","volume":"295","author":"A Fosang","year":"1993","journal-title":"Biochem J."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"17-20","DOI":"10.1016\/0014-5793(95)01539-6","article-title":"Degradation of cartilage aggrecan by collagenase-3 (MMP-13).","volume":"380","author":"A Fosang","year":"1996","journal-title":"FEBS Lett."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"578-586","DOI":"10.1196\/annals.1329.067","article-title":"Effects of curcumin (diferuloylmethane) on nuclear factor kappaB signaling in interleukin-1beta-stimulated chondrocytes.","volume":"1030","author":"G Schulze-Tanzil","year":"2004","journal-title":"Ann N Y Acad Sci."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"899-908","DOI":"10.1007\/s00011-009-0063-1","article-title":"Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes.","volume":"58","author":"M Mathy-Hartert","year":"2009","journal-title":"Inflamm Res."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"761-768","DOI":"10.1172\/JCI118475","article-title":"Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage.","volume":"97","author":"P Mitchell","year":"1996","journal-title":"J Clin Invest."},{"key":"ref-40","first-page":"79-87","article-title":"Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage.","volume":"78","author":"S Ohta","year":"1998","journal-title":"Lab Invest."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"3244-3253","DOI":"10.1002\/art.22167","article-title":"Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase activation: implications for cartilage degradation in arthritis.","volume":"54","author":"H Barksby","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"19-35","DOI":"10.1007\/s10875-006-9066-7","article-title":"\"Spicing up\" of the immune system by curcumin.","volume":"27","author":"G Jagetia","year":"2007","journal-title":"J Clin Immunol."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"64-71","DOI":"10.1248\/cpb.55.64","article-title":"Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors.","volume":"55","author":"N Handler","year":"2007","journal-title":"Chem Pharm Bull (Tokyo)."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"1671-1679","DOI":"10.1093\/carcin\/bgh165","article-title":"Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase.","volume":"25","author":"J Hong","year":"2004","journal-title":"Carcinogenesis."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"75-79","DOI":"10.1016\/S0014-5793(03)00672-0","article-title":"IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase.","volume":"547","author":"M Catley","year":"2003","journal-title":"FEBS Lett."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"1173-1180","DOI":"10.1007\/s11745-997-0151-8","article-title":"Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages.","volume":"32","author":"B Joe","year":"1997","journal-title":"Lipids."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"1645-1651","DOI":"10.1111\/j.1745-7254.2007.00651.x","article-title":"Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia.","volume":"28","author":"C Jin","year":"2007","journal-title":"Acta Pharmacol Sin."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"R135","DOI":"10.1186\/ar2024","article-title":"Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is a mechanosensitive gene.","volume":"8","author":"M Gosset","year":"2006","journal-title":"Arthritis Res Ther."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"1292-1301","DOI":"10.1002\/art.10892","article-title":"Proteoglycan degradation after injurious compression of bovine and human articular cartilage in vitro: interaction with exogenous cytokines.","volume":"48","author":"P Patwari","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"3404-3418","DOI":"10.1002\/art.11333","article-title":"Oncostatin M in combination with tumor necrosis factor alpha induces cartilage damage and matrix metalloproteinase expression in vitro and in vivo.","volume":"48","author":"W Hui","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref-51","first-page":"1894-1900","article-title":"Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer.","volume":"7","author":"R Sharma","year":"2001","journal-title":"Clin Cancer Res."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1477-3155-5-3","article-title":"Polymeric nanoparticle-encapsulated curcumin (\"nanocurcumin\"): a novel strategy for human cancer therapy.","volume":"5","author":"S Bisht","year":"2007","journal-title":"J 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.2044.r1736, Oliver Grundmann, University of Florida, Gainesville, FL, USA, 06 Sep 2013, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-147\/v2#referee-response-1736","order":0,"name":"referee-response-1736","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ali Mobasheri<\/b>; <i>Posted: 09 Sep 2013<\/i>; The authors wish to thank Dr.&nbsp;Grundmann for his insightful comments and for approving the second version of the paper.","URL":"https:\/\/f1000research.com\/articles\/2-147\/v2#referee-comment-549","order":1,"name":"referee-comment-549","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.2044.r1753, Stefan Toegel, Medical University of Vienna, Vienna, Austria, 09 Sep 2013, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-147\/v2#referee-response-1753","order":2,"name":"referee-response-1753","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Ali Mobasheri<\/b>; <i>Posted: 09 Sep 2013<\/i>; The authors wish to thank Dr.&nbsp;Toegel for the constructive comments that have helped us improve the manuscript and for approving the second version of the paper.","URL":"https:\/\/f1000research.com\/articles\/2-147\/v2#referee-comment-550","order":3,"name":"referee-comment-550","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work received major financial support from the Biotechnology and Biological Sciences Research Council through the Industrial CASE Studentship programme (Grant Number: BBS\/S\/M\/2006\/13141) and minor financial support from the WALTHAM Centre for Pet Nutrition. The BBSRC had no involvement in the study design, data collection, analysis and interpretation. The decision to submit the paper for publication was not influenced by the funding bodies.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}