Cheng Liang, Zeng Guoqing, Liu Zejun, Zhang Bing, Cui Xu, Zhao Honghai, Zheng Xinpeng, Song Gang, Kang Jian, Xia Chun
Zhongshan Hospital, University of Xiamen, Xiamen, Fujian, China.
Taiping People's Hospital of Dongguan, University of Jinan, Dongguan, Guangdong, China.
J Cell Mol Med. 2015 Aug;19(8):1877-86. doi: 10.1111/jcmm.12559. Epub 2015 Mar 5.
Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.
尽管对山茱萸环烯醚萜苷的主要活性成分莫诺苷的多方面作用进行了广泛研究，但莫诺苷对骨关节炎（OA）软骨细胞的影响仍知之甚少。在此，我们研究了莫诺苷对培养的人OA软骨细胞和大鼠OA实验模型的影响。结果表明，莫诺苷提高了人OA软骨细胞的活力以及增殖细胞核抗原表达（PCNA）、II型胶原蛋白和聚集蛋白聚糖的水平，表明莫诺苷促进了软骨细胞存活和基质合成。此外，不同剂量的莫诺苷激活了人OA软骨细胞中的蛋白激酶B（AKT）和细胞外信号调节激酶（ERK），进而分别触发了AKT/S6和ERK/P70S6K/S6信号通路。PI3K/AKT抑制剂LY294002或MEK/ERK抑制剂U0126减弱了莫诺苷对人OA软骨细胞的作用，表明AKT和ERK的激活有助于莫诺苷对人OA软骨细胞的调节。此外，在大鼠OA实验模型中，关节内注射莫诺苷可提高软骨基质中蛋白聚糖的水平和关节软骨的厚度，同时AKT和ERK的激活增加。因此，莫诺苷对OA软骨细胞具有软骨保护作用，可能具有治疗OA的潜力。
