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

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.