Zhang Chun, Yu Ling, Zhou Yan, Zhao Qi, Liu Shi-Qing
Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, 430060, China.
Glycoconj J. 2016 Oct;33(5):735-44. doi: 10.1007/s10719-016-9667-1. Epub 2016 May 13.
The preventive and therapeutic effects of chitosan oligosaccharides (COS) on osteoarthritis (OA) have been rarely investigated. In this study, the protective effects of COS against IL-1β-induced chondrocyte apoptosis were evaluated and the underlying mechanisms were elucidated. Results showed that COS not only inhibited cell apoptosis in a dose-dependent manner but also ameliorated IL-1β-induced nuclear chromatin damage and mitochondrial membrane potential in chondrocytes. In IL-1β-treated chondrocytes, COS downregulated the expression of Bax and caspase-3 but upregulated the expression of Bcl-2 by inhibiting the phosphorylated p38 mitogen-activated protein kinase (MAPK). COS inhibited the mRNA expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-13 (MMP-13) and enhanced the mRNA expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1). These results suggested that COS effectively inhibits the IL-1β-induced apoptosis of chondrocytes by activating the p38 MAPK signaling pathway. COS may also be used as a unique biological agent to prevent and treat OA.
壳寡糖（COS）对骨关节炎（OA）的预防和治疗作用鲜有研究。本研究评估了COS对白细胞介素-1β（IL-1β）诱导的软骨细胞凋亡的保护作用，并阐明了其潜在机制。结果表明，COS不仅以剂量依赖的方式抑制细胞凋亡，还改善了IL-1β诱导的软骨细胞核染色质损伤和线粒体膜电位。在IL-1β处理的软骨细胞中，COS通过抑制磷酸化的p38丝裂原活化蛋白激酶（MAPK）下调Bax和半胱天冬酶-3的表达，但上调Bcl-2的表达。COS抑制诱导型一氧化氮合酶（iNOS）和基质金属蛋白酶-13（MMP-13）的mRNA表达，并增强金属蛋白酶组织抑制剂-1（TIMP-1）的mRNA表达。这些结果表明，COS通过激活p38 MAPK信号通路有效抑制IL-1β诱导的软骨细胞凋亡。COS也可能作为一种独特的生物制剂用于预防和治疗OA。
