Vanillic acid attenuates cartilage degeneration by regulating the MAPK and PI3K/AKT/NF-κB pathways
Vanillic acid attenuates cartilage degeneration by regulating the MAPK and PI3K/AKT/NF-κB pathways
复制标题
香草酸通过调节 MAPK 和 PI3K/AKT/NF-kappa B 通路减轻软骨退化
DOI：
10.1016/j.ejphar.2019.172481
复制
发表时间：
2019-09-15
影响因子：
5
通讯作者：
You, Hongbo
中科院分区：
文献类型：
--
作者：
Huang, Xiaojian;Xi, Yang;You, Hongbo
骨关节炎(OA)是一种常见的关节病，其特征是软骨丢失和破坏。香草酸(VA)是一种广为人知的黄酮类化合物，具有多种药理活性。然而，香草酸对关节软骨破坏的作用和OA的发病机制仍不清楚。本研究观察到，在体内和体外，维生素A都能延缓骨性关节炎的进展。VA可抑制炎症反应，包括环氧合酶-2(COX-2)、诱导型一氧化氮合酶(INOS)、基质金属蛋白酶(MMPs)和阿奇卡那酶-2(ADAMTS5)的表达。此外，VA还降低了肥大软骨细胞的主要标志物胶原X、Runx2和血管内皮生长因子(VEGFA)。此外，VA还可抑制IL-1β(IL-1β)刺激的胶原蛋白2和聚集素的破坏。此外，VA浓度依赖地抑制IL-1β诱导的高迁移率族蛋白1(HMGB1)的产生，HMGB1是一种典型的损伤相关分子模式(DAMP)分子，在OA中具有强烈的促炎作用。同时，我们发现VA抑制了IL-1β诱导的MAPK和PI3K/AKT/NF-kappaB通路的激活。在体内，VA减缓了大鼠骨性关节炎模型的进展。总而言之，我们的结果表明，VA有可能成为一种新的OA治疗候选方案。
Osteoarthritis (OA) is a frequently seen arthropathy that features cartilage loss and destruction. Vanillic acid (VA), is a well-known flavonoid, which possesses various pharmacological activities. However, the effects of Vanillic acid on articular cartilage destruction and the pathogenesis of OA remain unknown. The present study observed that VA attenuated OA progression in vivo and vitro. VA inhibited the expression of inflammation responses, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs) and aggrecanase - 2(ADAMTS5). Moreover, the major markers of hypertrophic chondrocytes such as Collagen X, Runt related transcription factor 2 (Runx2) and Vascular endothelial growth factor (VEGFA) were also reduced by VA. In addition, the interleukin-1 beta (IL-1 beta) -stimulated collagen 2 and aggrecan destruction were suppressed by VA. Moreover, VA concentration -dependently inhibited IL-1 beta induced production of High-mobility group box 1 (HMGB1), a classic damage-associated molecular pattern (DAMP) molecule with strong pro-inflammatory effects in OA. Meanwhile, we revealed that VA suppressed the IL-1 beta induced activation of MAPK and PI3K/AKT/NF-kappa B pathways. In vivo, VA alleviated osteoarthritis progression in a rat OA model. Collectively, our results demonstrate that VA could potentially be a new candidate for OA therapy.