Emodin Attenuates the ECM Degradation and Oxidative Stress of Chondrocytes through the Nrf2/NQO1/HO-1 Pathway to Ameliorate Rat Osteoarthritis

Abstract

Osteoarthritis (OA) substantially reduces the quality of life of the elderly. OA therapy remains a challenge since no treatment options for its causes are so far available. Over recent years, researchers have speculated that emodin may represent a potential treatment strategy for OA. However, it remains unclear whether the mechanism of action of emodin is associated with the inhibition of OA-induced oxidative stress. In the present study, the potential antioxidant mechanism of action of emodin and its protective properties against the development of OA were investigated both in vitro and in vivo. In vitro, emodin inhibited the production of reactive oxygen species (ROS) in chondrocytes induced by hydrogen peroxide (H2O2) and reduced the expression of matrix metalloproteinase (MMP)3 and MMP13 in a concentration-dependent manner. It was found that emodin upregulated the Nrf2/NQO1/HO-1 pathway, thereby attenuating the effects of oxidative stress caused by OA. In a rat model of posttraumatic OA induced by anterior cruciate ligament transection (ACLT), emodin reduced the extent of joint swelling. Emodin attenuated oxidative damage in the cartilage by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity, reducing malondialdehyde (MDA) concentration and inhibiting the expression of the extracellular matrix (ECM) degradation biomarkers cartilage oligomeric matrix protein (COMP), and C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II), thereby reducing cartilage damage. In summary, the present study indicates that emodin reduces ECM degradation and oxidative stress in chondrocytes via the Nrf2/NQO1/HO-1 pathway, thereby ameliorating OA in rats.