Protein kinase B and extracellular signal-regulated kinase contribute to the chondroprotective effect of morroniside on osteoarthritis chondrocytes.
Protein kinase B and extracellular signal-regulated kinase contribute to the chondroprotective effect of morroniside on osteoarthritis chondrocytes.
复制标题
蛋白激酶 B 和细胞外信号调节激酶有助于莫诺苷对骨关节炎软骨细胞的软骨保护作用。
DOI：
10.1111/jcmm.12559
复制
发表时间：
2015-08
影响因子：
5.3
通讯作者：
Xia C
中科院分区：
文献类型：
--
作者：
Cheng L;Zeng G;Liu Z;Zhang B;Cui X;Zhao H;Zheng X;Song G;Kang J;Xia C
尽管对莫诺苷（山茱萸中环烯醚萜苷的主要活性成分）的多方面作用进行了广泛的研究，但莫诺苷对骨关节炎（OA）软骨细胞的作用仍知之甚少。在这里，我们研究了莫诺苷对培养的人 OA 软骨细胞和 OA 大鼠实验模型的影响。结果表明，莫诺苷增强了人OA软骨细胞的细胞活力和增殖细胞核抗原表达（PCNA）、II型胶原和蛋白聚糖的水平，表明莫诺苷促进软骨细胞存活和基质合成。此外，不同剂量的莫诺苷激活人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AKT/S6和ERK/P70S6K/S6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在人OA软骨细胞中的调节。此外，关节内注射莫诺苷可升高大鼠OA实验模型中软骨基质中的蛋白多糖水平和关节软骨厚度，并增加AKT和ERK活化。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。
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.