Curcumin inhibits pro-inflammatory mediators and metalloproteinase-3 production by chondrocytes
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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.
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.
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.
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.
KeywordsCurcumin Inflammation Arthritis Chondrocytes Cartilage
The work was supported by an educational grant from BioXtract. Christelle Sanchez is a Postdoctoral Researcher of the National Fund for Scientific Research (FNRS, Belgium). The authors extend their appreciation to Paul Simonis and Murielle Lemestre (Centre Hospitalier Universitaire de Liège) for their skillful technical assistance.
- 6.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.CrossRefPubMedGoogle Scholar
- 9.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.CrossRefPubMedGoogle Scholar
- 20.Deodhar SD, Sethi R, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Ind J Med Res. 1980;71:632–4.Google Scholar
- 39.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.PubMedGoogle Scholar