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

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-1 beta (IL-1 beta, 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 (LXR alpha) 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-1 beta. Besides, Vaspin promoted the expression of LXRa 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 LXR alpha 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/LXR alpha. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage.

Automated summary

This study explored the role of Vaspin and cholesterol metabolism in osteoarthritis (OA) through in vitro and in vivo experiments. It was found that Vaspin reversed IL-1 beta-induced expression changes in chondrocytes, but miR155 mimics could reverse the effects on cholesterol efflux pathway. Furthermore, in a rat OA model, the decreased expression of cholesterol efflux related genes was associated with reduced Vaspin levels and increased miR155 expression in OA knee cartilage.