Icariin Activates Autophagy via Down-Regulation of the NF-κB Signaling-Mediated Apoptosis in Chondrocytes

Abstract

Osteoarthritis (OA) is a common chronic and degenerative joint condition that is mainly characterized by cartilage degradation, osteophyte formation, and joint stiffness. The NF-κB signaling pathway in inflammation, autophagy, and apoptosis plays a prominent role in the progression of OA. Icariin, a prenylated flavonol glycoside extracted from Epimedium, have been proven to exert anti-osteoporotic and anti-inflammatory effects in OA. However, the action mechanisms of its effect on chondrocytes have yet to be elucidated. In the present study, we demonstrated that the <i>in vitro</i> therapeutic effects of icariin on rat chondrocytes in a dose-dependent manner. We found that TNF-α induced the production of IL-1, IL-6, IL-12, reactive oxygen species (ROS), nitric oxide (NO), Caspase-3, and Caspase-9 in chondrocytes. We also provided evidence that TNF-α inhibited autophagy markers (Atg 5, Atg 7) and prevented LC3 I translate to LC3 II. Furthermore, TNF-α induced matrix metalloproteinase (MMP)3 and MMP9 expression. The negative effects of TNF-α on chondrocytes can be partially blocked by treating with icariin or ammonium pyrrolidinedithiocarbamate (PDTC, an NF-κB inhibitor). The present study data also suggested that icariin suppressed both TNF-α-stimulated p65 nuclear translocation and IκBα protein degradation. These results indicated that icariin protected against OA by suppressing inflammatory cytokines and apoptosis, through activation of autophagy via NF-κB inhibition. In conclusion, icariin appears to favorably modulate autophagy and apoptosis in chondrocytes making it a promising compound for cartilage tissue engineering in the treatment of OA.