Shakibaei Mehdi, Schulze-Tanzil Gundula, John Thilo, Mobasheri Ali
Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 11, 80336 Munich, Germany.
Ann Anat. 2005 Nov;187(5-6):487-97. doi: 10.1016/j.aanat.2005.06.007.
Interleukin 1beta (IL-1beta) is a pleiotropic pro-inflammatory cytokine that plays a key role in mediating cartilage degradation in osteoarticular disorders such as osteoarthritis (OA) and rheumatoid arthritis (RA). At the cellular level, IL-1beta activates matrix degrading enzymes, down-regulates expression of matrix components and induces chondrocyte apoptosis. Curcumin (diferuloylmethane) is an anti-inflammatory phytochemical agent that has recently been shown to antagonize the pro-inflammatory effects of cytokines in chondrocytes and other cells. To test the hypothesis that curcumin also protects chondrocytes from morphological alterations induced by IL-1beta, we investigated its in vitro effects on apoptotic signalling proteins and key cartilage-specific matrix components in IL-1beta-stimulated chondrocytes. Human articular chondrocytes were pre-treated with 10 ng/mI IL-1beta alone for 30 min before being co-treated with IL-1beta and 50 microM curcumin for 5, 15 or 30 min, respectively. The ultrastructural morphology of chondrocytes was investigated by transmission electron microscopy. The production of collagen type II, the adhesion and signal transduction receptor beta1-integrin, the apoptosis marker activated caspase-3 was analysed by immunohistochemistry, immunoelectron microscopy and Western blotting. Transmission electron microscopy of chondrocytes stimulated with IL-1beta revealed early degenerative changes which were relieved by curcumin co-treatment. The suppression of collagen type II and beta1-integrin synthesis by IL-1beta was inhibited by curcumin. Additionally, curcumin antagonized IL-1beta-induced caspase-3 activation in a time-dependent manner. This study clearly demonstrates that curcumin exerts anti-apoptotic and anti-catabolic effects on IL-1beta-stimulated articular chondrocytes. Therefore curcumin may have novel therapeutic potential as an adjunct nutraceutical chondroprotective agent for treating OA and related osteoarticular disorders.
白细胞介素1β（IL-1β）是一种多效性促炎细胞因子，在介导骨关节炎（OA）和类风湿关节炎（RA）等骨关节疾病中的软骨降解过程中起关键作用。在细胞水平上，IL-1β激活基质降解酶，下调基质成分的表达并诱导软骨细胞凋亡。姜黄素（二阿魏酰甲烷）是一种抗炎植物化学剂，最近已显示出可拮抗细胞因子在软骨细胞和其他细胞中的促炎作用。为了验证姜黄素也能保护软骨细胞免受IL-1β诱导的形态学改变这一假设，我们研究了其对IL-1β刺激的软骨细胞中凋亡信号蛋白和关键软骨特异性基质成分的体外作用。人关节软骨细胞先单独用10 ng/mL IL-1β预处理30分钟，然后分别与IL-1β和50 μM姜黄素共同处理5、15或30分钟。通过透射电子显微镜研究软骨细胞的超微结构形态。通过免疫组织化学、免疫电子显微镜和蛋白质印迹分析II型胶原蛋白、黏附及信号转导受体β1整合素的产生以及凋亡标志物活化的半胱天冬酶-3。用IL-1β刺激的软骨细胞的透射电子显微镜检查显示出早期退行性变化，而姜黄素共同处理可缓解这些变化。姜黄素抑制了IL-1β对II型胶原蛋白和β1整合素合成的抑制作用。此外,姜黄素以时间依赖性方式拮抗IL-1β诱导的半胱天冬酶-3活化。本研究清楚地表明，姜黄素对IL-1β刺激的关节软骨细胞具有抗凋亡和抗分解代谢作用。因此，姜黄素作为一种辅助营养软骨保护剂用于治疗OA和相关骨关节疾病可能具有新的治疗潜力。
