Pravastatin Reduces Matrix Metalloproteinases Expression and Promotes Cholesterol Efflux in Osteoarthritis Chondrocytes.

Abstract

Background Chondrocyte metabolic disorder plays an important role in the development of osteoarthritis (OA). The use of statins in the treatment of OA has also been widely studied, but the mechanism is still confusing. The present study aims to investigate the effects of statin on osteoarthritis chondrocytes and its underlying mechanism. Major findings. An untargeted metabolomics study revealed that the treatment of statins significantly changed the metabolites of articular cartilage tissues collected from female osteoarthritis patients, and might be involved in the glycerophospholipid metabolism pathway. In vitro study showed that 5–50 μmol/L of pravastatin exerts no cytotoxicity on human chondrocytes. Besides, 50 μmol/L of pravastatin caused a significant decrease in the expression of matrix metalloproteinase (MMP)-1 and MPP-13, and intracellular cholesterol in interleukin-1β (IL-1β)-induced human chondrocytes. Furthermore, at both mRNA and protein levels, the expression of the proteins related to the cholesterol efflux pathway (liver X receptor and cholesterol efflux regulatory protein) were significantly up-regulated by 50 μmol/L of pravastatin in IL-1β-induced human chondrocytes. Conclusion Pravastatin can reduce the expression of MMPs in IL-1β-induced human chondrocytes and protect the chondrocyte matrix. The mechanism may be related to promoting the expression of proteins related to the cholesterol efflux pathway and reducing the level of cellular cholesterol.