Chen Yue-Yuan, Yan Xiao-Jie, Jiang Xiao-Hua, Lu Feng-Lai, Yang Xue-Rong, Li Dian-Peng
Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin, Guangxi 541006, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1461. doi: 10.3892/etm.2021.10896. Epub 2021 Oct 20.
Aberrant destruction of the articular extracellular matrix (ECM) has been considered to be one of the pathological features of osteoarthritis (OA) which results in chondrocyte changes and articular cartilage degeneration. The MAPK signaling pathway serves a key role by releasing cartilage-degrading enzymes from OA chondrocytes. However, the use of MAPK inhibitors for OA is hindered by their potential long-term toxicity. Vicenin 3 is one of the major components of the Jian-Gu injection which is effective in the clinical treatment of OA. However, its potential impact on OA remain poorly understood. Therefore, the present study aimed to assess the effects of vicenin 3 on interleukin (IL)-1β-treated SW1353 chondrocytes, which mimic the microenvironment of OA. These chondrocytes were pretreated with vicenin 3 (0, 5 and 20 µM) for 1 h and subsequently stimulated with IL-1β (10 ng/ml) for 24 h. Nitric oxide (NO) production was measured using the Griess reaction, whereas the production of prostaglandin E2 (PGE2), matrix metalloproteinases (MMPs), A disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs), collagen type II and aggrecan were measured using ELISA. The mRNA expression of MMPs and ADAMTSs were measured using reverse transcription-quantitative PCR. The protein expression levels of MAPK were measured using western blotting. Vicenin 3 was found to significantly inhibit IL-1β-induced production of NO and PGE. Increments in the expression levels of MMP-1, MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 induced by IL-1β, in addition to the IL-1β-induced degradation of collagen type II and aggrecan, were all reversed by vicenin 3 treatment. Furthermore, vicenin 3 suppressed IL-1β-stimulated MAPK activation, an effect that was similar to that exerted by SB203580, a well-known p38 MAPK inhibitor. In conclusion, vicenin 3 may confer therapeutic potential similar to that of the p38 MAPK inhibitor for the treatment of OA.
关节细胞外基质(ECM)的异常破坏被认为是骨关节炎(OA)的病理特征之一,这会导致软骨细胞变化和关节软骨退变。丝裂原活化蛋白激酶(MAPK)信号通路通过从OA软骨细胞中释放软骨降解酶发挥关键作用。然而,MAPK抑制剂用于OA治疗受到其潜在长期毒性的阻碍。维西宁3是健骨注射液的主要成分之一,在OA的临床治疗中有效。然而,其对OA的潜在影响仍知之甚少。因此,本研究旨在评估维西宁3对白细胞介素(IL)-1β处理的SW1353软骨细胞的影响,这些细胞模拟了OA的微环境。这些软骨细胞用维西宁3(0、5和20 μM)预处理1小时,随后用IL-1β(10 ng/ml)刺激24小时。使用格里斯反应测量一氧化氮(NO)的产生,而使用酶联免疫吸附测定(ELISA)测量前列腺素E2(PGE2)、基质金属蛋白酶(MMPs)、含血小板反应蛋白基序的解聚素样金属蛋白酶(ADAMTSs)、II型胶原蛋白和聚集蛋白聚糖的产生。使用逆转录定量聚合酶链反应(RT-qPCR)测量MMPs和ADAMTSs的mRNA表达。使用蛋白质免疫印迹法测量MAPK的蛋白表达水平。发现维西宁3可显著抑制IL-1β诱导的NO和PGE产生。维西宁3处理可逆转IL-1β诱导的MMP-1、MMP-3、MMP-13、ADAMTS-4和ADAMTS-5表达水平的增加,以及IL-1β诱导的II型胶原蛋白和聚集蛋白聚糖的降解。此外,维西宁3抑制IL-1β刺激的MAPK激活,其作用与著名的p38 MAPK抑制剂SB203580相似。总之,维西宁3可能具有与p38 MAPK抑制剂相似的治疗潜力,可用于OA的治疗。