Orthopaedic Research Lab, University of Virginia, Charlottesville, VA, USA.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, China.
Int J Nanomedicine. 2019 Jun 6;14:4145-4155. doi: 10.2147/IJN.S202466. eCollection 2019.
There is emerging evidence which suggests that cellular ROS including nitric oxide (NO) are important mediators for inflammation and osteoarthritis (OA). Water-soluble polyhydroxylated fullerene C60 (fullerol) nanoparticle has been demonstrated to have an outstanding ability to scavenge ROS. The objective of this study is to assess the effects of fullerol on inflammation and OA by in vitro and in vivo studies. For in vitro experiments, primary mouse peritoneal macrophages and a macrophage cell line RAW264.7 were stimulated to inflammatory phenotypes by lipopolysaccharide (LPS) in the presence of fullerol. For the animal study, OA model was created by intra-articular injection of monoiodoacetate into the knee joints of rats and fullerol was intravenously injected immediately after OA induction. NO production and pro-inflammatory gene expression induced by LPS was significantly diminished by fullerol in both macrophage cell types. Meanwhile, fullerol could remarkably reduce phosphorylation of p38 mitogen-activated protein kinase, and protein level of transcription factors nuclear factor-kappaB and forkhead box transcription factor 1 within the nucleus. The animal study delineated that systematic administration of fullerol prevented OA, inhibiting inflammation of synovial membranes and the damage toward the cartilage chondrocytes in the OA joints. Antioxidative fullerol may have a potential therapeutic application for OA.
有新的证据表明，细胞内的活性氧（ROS）包括一氧化氮（NO），是炎症和骨关节炎（OA）的重要介质。水溶性多羟基富勒烯 C60（富勒醇）纳米颗粒已被证明具有出色的清除 ROS 的能力。本研究的目的是通过体外和体内研究来评估富勒醇对炎症和 OA 的影响。在体外实验中，用富勒醇刺激原代小鼠腹腔巨噬细胞和巨噬细胞系 RAW264.7，使其在脂多糖（LPS）的存在下表现出炎症表型。在动物研究中，通过向大鼠膝关节内注射单碘乙酸盐来创建 OA 模型，并在 OA 诱导后立即静脉注射富勒醇。富勒醇可显著降低两种巨噬细胞类型中 LPS 诱导的 NO 产生和促炎基因表达。同时，富勒醇可显著降低丝裂原活化蛋白激酶 p38 的磷酸化水平，以及核内转录因子核因子-κB 和叉头框转录因子 1 的蛋白水平。动物研究表明，系统给予富勒醇可预防 OA，抑制 OA 关节滑膜炎症和软骨细胞损伤。抗氧化富勒醇可能具有治疗 OA 的潜在应用价值。
