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牛膝多糖通过 lncRNA NEAT1/miR-377-3p 通路缓解骨关节炎内质网应激。

Achyranthes bidentata polysaccharides alleviate endoplasmic reticulum stress in osteoarthritis via lncRNA NEAT1/miR-377-3p pathway.

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, Fujian 350122, China; Fujian Provincial Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, Fujian 350122, China.

Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350003, China; Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, Fujian 350003, China.

出版信息

Biomed Pharmacother. 2022 Oct;154:113551. doi: 10.1016/j.biopha.2022.113551. Epub 2022 Aug 19.

Abstract

Endoplasmic reticulum stress (ERS) has been identified to be an important factor leading to chondrocyte apoptosis in osteoarthritis (OA). Previous studies have confirmed that Achyranthes bidentata polysaccharides (ABPS) can inhibit chondrocyte apoptosis; however, the mechanism of action of ABPS on chondrocyte ERS remains unclear. Thus in this study, we aim to investigate whether ABPS could inhibit OA-associated chondrocyte apoptosis by regulating ERS, especially by observing the relationship between the lncRNA NEAT1 and miR-377-3p, to explore further the protective mechanism of ABPS in OA. In vitro and in vivo experiments showed that ABPS inhibited chondrocyte ERS by regulating the expression of lncRNA NEAT1 and miR-377-3p. Moreover, both lncRNA NEAT1 silencing and miR-377-3p inhibition could attenuate the therapeutic effect of ABPS on ERS. Dual-luciferase results indicated that miR-377-3p targets the lncRNA NEAT1 gene in mouse chondrocytes. Therefore, we concluded that ABPS could inhibit thapsigargin (TG)-induced chondrocyte ERS through the lncRNA NEAT1/miR-377-3p axis.

摘要

内质网应激(ERS)已被确定为导致骨关节炎(OA)软骨细胞凋亡的重要因素。先前的研究已经证实,牛膝多糖(ABPS)可以抑制软骨细胞凋亡;然而,ABPS 对软骨细胞 ERS 的作用机制尚不清楚。因此,在这项研究中,我们旨在探讨 ABPS 是否可以通过调节 ERS 来抑制与 OA 相关的软骨细胞凋亡,特别是通过观察 lncRNA NEAT1 和 miR-377-3p 之间的关系,进一步探讨 ABPS 在 OA 中的保护机制。体外和体内实验表明,ABPS 通过调节 lncRNA NEAT1 和 miR-377-3p 的表达抑制软骨细胞 ERS。此外,lncRNA NEAT1 沉默和 miR-377-3p 抑制均可减弱 ABPS 对 ERS 的治疗作用。双荧光素酶结果表明,miR-377-3p 靶定小鼠软骨细胞中的 lncRNA NEAT1 基因。因此,我们得出结论,ABPS 可以通过 lncRNA NEAT1/miR-377-3p 轴抑制他普西苷(TG)诱导的软骨细胞 ERS。

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