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壳寡糖通过P38丝裂原活化蛋白激酶信号通路抑制白细胞介素-1β诱导的软骨细胞凋亡。

Chitosan oligosaccharides inhibit IL-1β-induced chondrocyte apoptosis via the P38 MAPK signaling pathway.

作者信息

Zhang Chun, Yu Ling, Zhou Yan, Zhao Qi, Liu Shi-Qing

机构信息

Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan, 430060, China.

出版信息

Glycoconj J. 2016 Oct;33(5):735-44. doi: 10.1007/s10719-016-9667-1. Epub 2016 May 13.

Abstract

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.

摘要

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。

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