Tao Ran, Wang Shitao, Xia Xiaopeng, Wang Youhua, Cao Yi, Huang Yuejiao, Xu Xinbao, Liu Zhongbing, Liu Peichao, Tang Xiaohang, Liu Chun, Shen Gan, Zhang Dongmei
Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Inflammation. 2015 Aug;38(4):1546-55. doi: 10.1007/s10753-015-0129-x.
Osteoarthritis (OA) is the most common arthritis and also one of the major causes of joint pain in elderly people. The aim of this study was to investigate the effects of pyrroloquinoline quinone (PQQ) on degenerated-related changes in osteoarthritis (OA). SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. PQQ was administrated into SW1353 cultures 1 h before IL-1β treatment. Amounts of MMP-1, MMP-13, P65, IκBα, ERK, p-ERK, P38, and p-P38 were measured via western blot. The production of NO was determined by Griess reaction assay and reflected by the iNOS level. Meniscal-ligamentous injury (MLI) was performed on 8-week-old rats to establish the OA rat model. PQQ was injected intraperitoneally 3 days before MLI and consecutively until harvest, and the arthritis cartilage degeneration level was assessed. The expressions of MMP-1 and MMP-13 were significantly downregulated after PQQ treatment compared with that in IL-1β alone group. NO production and iNOS expression were decreased by PQQ treatment compared with control group. Amounts of nucleus P65 were upregulated in SW1353 after stimulated with IL-1β, while PQQ significantly inhibited the translocation. In rat OA model, treatment with PQQ markedly decelerated the degeneration of articular cartilage. These findings suggested that PQQ could inhibit OA-related catabolic proteins MMPs expression, NO production, and thus, slow down the articular cartilage degeneration and OA progression. Owing to its beneficial effects, PQQ is expected to be a novel pharmacological application in OA clinical prevention and treatment in the near future.
骨关节炎(OA)是最常见的关节炎,也是老年人关节疼痛的主要原因之一。本研究的目的是探讨吡咯喹啉醌(PQQ)对骨关节炎(OA)退变相关变化的影响。用白细胞介素-1β(IL-1β)刺激SW1353细胞,在体外建立软骨细胞损伤模型。在IL-1β处理前1小时将PQQ加入SW1353培养物中。通过蛋白质免疫印迹法检测基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-13(MMP-13)、P65、IκBα、细胞外信号调节激酶(ERK)、磷酸化细胞外信号调节激酶(p-ERK)、p38丝裂原活化蛋白激酶(P38)和磷酸化p38丝裂原活化蛋白激酶(p-P38)的含量。采用Griess反应法测定一氧化氮(NO)的产生,并通过诱导型一氧化氮合酶(iNOS)水平反映。对8周龄大鼠进行半月板韧带损伤(MLI)以建立OA大鼠模型。在MLI前3天腹腔注射PQQ,并持续至处死,评估关节炎软骨退变程度。与单独使用IL-1β组相比,PQQ处理后MMP-1和MMP-13的表达明显下调。与对照组相比,PQQ处理降低了NO的产生和iNOS的表达。IL-1β刺激后SW1353细胞核内P65含量上调,而PQQ显著抑制其转位。在大鼠OA模型中,PQQ治疗显著减缓了关节软骨的退变。这些结果表明,PQQ可以抑制OA相关的分解代谢蛋白MMPs的表达和NO的产生,从而减缓关节软骨退变和OA进展。由于其有益作用,预计PQQ在不久将来可成为OA临床防治的新型药物应用。