Journal
LIFE SCIENCES
Volume 269, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119096
Keywords
Vaspin; Cholesterol metabolism; miR155; Cholesterol efflux pathway; Osteoarthritis
Funding
- Guangxi Natural Science Foundation youth Project [2018GXNSFBA281117]
- National Natural Science Foundation of China [81860274]
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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.
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.
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