Clutterbuck Abigail L, Mobasheri Ali, Shakibaei Mehdi, Allaway David, Harris Pat
Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, United Kingdom.
Ann N Y Acad Sci. 2009 Aug;1171:428-35. doi: 10.1111/j.1749-6632.2009.04687.x.
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 kappaB-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-1beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1beta at either 10 ng/mL (n= 3) or 25 ng/mL (n= 3) and curcumin (0.1 micromol/L, 0.5 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 micromol/L) significantly reduced IL-1beta-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-1beta-stimulated chondrocytes.
骨关节炎（OA）是一种滑膜关节的退行性和炎症性疾病，其特征是关节软骨丧失，人们对其天然疗法的兴趣与日俱增。姜黄素（二阿魏酰甲烷）是香料姜黄中的主要多酚类物质，姜黄源自植物姜黄的根茎。姜黄素具有强大的化学预防特性，已被证明能抑制包括软骨细胞在内的多种细胞类型中核因子κB介导的炎症信号传导。在本研究中，从八匹马的掌指关节和跖趾关节获取正常关节软骨，这些马因非研究目的而实施安乐死，以建立一个模拟骨关节炎中发生的炎症事件的外植体模型。最初，用浓度递增的促炎细胞因子IL-1β刺激软骨外植体（N = 8），以选择在该外植体模型中诱导软骨退变的有效剂量。然后将单独的软骨外植体与10 ng/mL（n = 3）或25 ng/mL（n = 3）的IL-1β以及姜黄素（0.1 μmol/L、0.5 μmol/L、1 μmol/L、10 μmol/L和100 μmol/L）共同处理。5天后，使用二甲基亚甲基蓝比色法评估外植体中糖胺聚糖（GAG）释放的百分比。姜黄素（100 μmol/L）在10 ng/mL时显著降低IL-1β刺激的外植体中GAG释放，平均降低20%，在25 ng/mL时降低27%，恢复到未刺激的对照水平（P < 0.001）。我们的结果表明，该外植体模型有效地模拟了骨关节炎中促炎细胞因子介导的关节软骨成分释放。此外，有证据表明，炎症性软骨外植体模型可用于研究姜黄素对IL-1β刺激的软骨细胞中炎症途径和基因表达的影响。
