Li Xiaodong, Feng Kai, Li Jiang, Yu Degang, Fan Qiming, Tang Tingting, Yao Xiao, Wang Xiaoqing
Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Nutrients. 2017 Apr 21;9(4):414. doi: 10.3390/nu9040414.
Osteoarthritis (OA) is an inflammatory disease of load-bearing synovial joints that is currently treated with drugs that exhibit numerous side effects and are only temporarily effective in treating pain, the main symptom of the disease. Consequently, there is an acute need for novel, safe, and more effective chemotherapeutic agents for the treatment of osteoarthritis and related arthritic diseases. Curcumin, the principal curcuminoid and the most active component in turmeric, is a biologically active phytochemical. Evidence from several recent in vitro studies suggests that curcumin may exert a chondroprotective effect through actions such as anti-inflammatory, anti-oxidative stress, and anti-catabolic activity that are critical for mitigating OA disease pathogenesis and symptoms. In the present study, we investigated the protective mechanisms of curcumin on interleukin 1β (IL-1β)-stimulated primary chondrocytes in vitro. The treatment of interleukin (IL)-1β significantly reduces the cell viability of chondrocytes in dose and time dependent manners. Co-treatment of curcumin with IL-1β significantly decreased the growth inhibition. We observed that curcumin inhibited IL-1β-induced apoptosis and caspase-3 activation in chondrocytes. Curcumin can increase the expression of phosphorylated extracellular signal-regulated kinases 1/2 (ERK1/2), autophagy marker light chain 3 (LC3)-II, and Beclin-1 in chondrocytes. The expression of autophagy markers could be decreased when the chondrocytes were incubated with ERK1/2 inhibitor U0126. Our results suggest that curcumin suppresses apoptosis and inflammatory signaling through its actions on the ERK1/2-induced autophagy in chondrocytes. We propose that curcumin should be explored further for the prophylactic treatment of osteoarthritis in humans and companion animals.
骨关节炎（OA）是一种发生在负重滑膜关节的炎症性疾病，目前用于治疗该病的药物存在诸多副作用，且仅能暂时缓解疼痛这一主要症状。因此，迫切需要新型、安全且更有效的化疗药物来治疗骨关节炎及相关关节炎疾病。姜黄素是姜黄中的主要姜黄素类化合物和最具活性的成分，是一种具有生物活性的植物化学物质。最近的几项体外研究证据表明，姜黄素可能通过抗炎、抗氧化应激和抗分解代谢等作用发挥软骨保护作用，这些作用对于减轻骨关节炎疾病的发病机制和症状至关重要。在本研究中，我们在体外研究了姜黄素对白介素1β（IL-1β）刺激的原代软骨细胞的保护机制。白介素（IL）-1β处理以剂量和时间依赖性方式显著降低软骨细胞的活力。姜黄素与IL-1β共同处理可显著降低生长抑制作用。我们观察到姜黄素抑制软骨细胞中IL-1β诱导的细胞凋亡和半胱天冬酶-3激活。姜黄素可增加软骨细胞中磷酸化细胞外信号调节激酶1/2（ERK1/2）、自噬标志物轻链3（LC3）-II和Beclin-1的表达。当软骨细胞与ERK1/2抑制剂U0126孵育时，自噬标志物的表达会降低。我们的结果表明，姜黄素通过对软骨细胞中ERK1/2诱导的自噬作用来抑制细胞凋亡和炎症信号传导。我们建议应进一步探索姜黄素用于人类和伴侣动物骨关节炎的预防性治疗。
