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

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

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.

Keywords: Cholesterol efflux pathway; Cholesterol metabolism; Osteoarthritis; Vaspin; miR155.

MeSH terms

  • Animals
  • Arthritis, Experimental / etiology
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Chondrocytes
  • Female
  • Gene Expression Regulation
  • Liver X Receptors / genetics
  • Liver X Receptors / metabolism*
  • MicroRNAs / genetics*
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology*
  • Rats
  • Rats, Wistar
  • Serpins / genetics
  • Serpins / metabolism*
  • Signal Transduction

Substances

  • Liver X Receptors
  • MIRN155 microRNA, rat
  • MicroRNAs
  • Nr1h3 protein, rat
  • Serpina12 protein, rat
  • Serpins
  • Cholesterol