脂联素通过 miR155/LXRα 调节软骨胆固醇代谢，并参与大鼠骨关节炎的发生。

Vaspin regulated cartilage cholesterol metabolism through miR155/LXRα and participated in the occurrence of osteoarthritis in rats.

机构信息

Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Department of Joint Osteopathy, Guangxi Liuzhou Workers Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545000, China.

出版信息

Life Sci. 2021 Mar 15;269:119096. doi: 10.1016/j.lfs.2021.119096. Epub 2021 Jan 20.

DOI:10.1016/j.lfs.2021.119096

PMID:33482192

Abstract

AIMS

This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo.

MAIN METHODS

In vitro, chondrocytes were treated with interleukin-1β (IL-1β, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo, the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain.

KEY FINDINGS

In vitro, in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1β. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo, the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats.

SIGNIFICANCE

In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage.

摘要

目的

本研究旨在探讨内脏脂肪素（Vaspin）和胆固醇代谢在骨关节炎（OA）发生发展过程中的作用及其在体内外的作用机制。

方法

体外，用白细胞介素-1β（IL-1β，20ng/ml）联合不同浓度的 Vaspin 处理软骨细胞 48h。检测聚集蛋白聚糖（ACAN）、Ⅱ型胶原（Col2a1）、解整合素金属蛋白酶与凝血酶 3 型（ADAMTS）5 和基质金属蛋白酶 13（MMP13）的表达。体内，用木瓜蛋白酶诱导大鼠 OA 膝关节软骨，检测肝 X 受体（LXRα）和其他胆固醇流出相关基因的表达。

结果

体外，Vaspin 呈浓度依赖性逆转了 IL-1β引起的 ACAN 和 Col2a1 表达降低，以及 ADAMTS 5 和 MMP13 表达升高。此外，Vaspin 呈浓度依赖性促进软骨细胞中 LXRα和其他胆固醇流出相关基因的表达。然而，miR155 模拟物逆转了 Vaspin 诱导的软骨细胞胆固醇流出途径的表达变化。体内，用木瓜蛋白酶诱导大鼠 OA 膝关节软骨，LXRα和其他胆固醇流出相关基因的表达降低。此外，OA 大鼠膝关节软骨中 Vaspin 水平降低，miR155（miR155）表达增加。