期刊
NATURAL COMPOUNDS AND THEIR ROLE IN APOPTOTIC CELL SIGNALING PATHWAYS
卷 1171, 期 -, 页码 428-435出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1749-6632.2009.04687.x
关键词
osteoarthritis; cartilage; inflammation; polyphenol; equine; glycosaminoglycan; cytokine; curcumin
资金
- Biotechnology and Biological Sciences Research Council (BBSRC)
- WALTHAM Centre for Pet Nutrition (MARS) [BBSRC/S/M/2006/13141]
Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappa B-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalangeal joints of eight horses, euthanized for reasons other than research purposes, to establish an explant model mimicking the inflammatory events that occur in OA. Initially, cartilage explants (N = 8) were stimulated with increasing concentrations of the proinflammatory cytokine IL-1 beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1 beta at either 10 ng/mL (n = 3) or 25 ng/mL (n = 3) and curcumin (0.1 mu mol/L, 0.5 mu mol/L, 1 mu mol/L, 10 mu mol/L, and 100 mu mol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 mu mol/L) significantly reduced IL-1 beta-stimulated GAG release in the explants by an average of 20% at 10 ng/mL and 27% at 25 ng/mL back to unstimulated control levels (P < 0.001). Our results suggest that this explant model effectively simulates the proinflammatory cytokine-mediated release of articular cartilage components seen in OA. Furthermore, the evidence suggests that the inflammatory cartilage explant model is useful for studying the effects of curcumin on inflammatory pathways and gene expression in IL-1 beta-stimulated chondrocytes.
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