Icariin induces autophagy and apoptosis of chondrocytes by inhibiting NF-κB signaling pathway

Jun Xiong,Hui Zou,Yi Yu

doi:10.4314/tjpr.v19i9.8

Abstract

Purpose: To investigate the effect of icariin on autophagy and apoptosis of chondrocytes, and the associated mechanisms.Methods: The chondrocytes were randomly divided into control (PBS intervention), TNF-α intervention, icarin +TNF-α, and NF-κB inhibition +TNF-α, with 8 strains in each group. The levels of IL-1, IL-6 and IL-12 were assayed by ELISA. The mRNA and protein expressions of ATG5, ATG7, Bax and Bcl-2 cells were determined by polymerase chain reaction (PCR) and Western blotting, while protein expressions of p-p65 and IκBα were assayed using Western blotting.Results: In the cartilage tissue of rats in the icariin +TNF-α group and NF-κB inhibition +TNF-α group, IL-1, IL-6 and IL-12 levels were significantly lower than those in TNF-α treatment group (p < 0.05). The AATG5 mRNA and protein in cartilage tissues of rats in icariin +TNF-α and NF-κB inhibition +TNF-α groups were significantly higher than those in TNF-α group. Bax mRNA and protein in cartilage tissues of icariin +TNF-α and NF-κB inhibition +TNF-α groups were downregulated, relative to TNF-α group; on the other hand, Bcl-2 mRNA and protein were significantly higher than those of TNF-α group (p < 0.05). In the cartilage tissues of Icarin +TNF-α, NF-κB inhibition +TNF-α groups, P-p65 protein was significantly lower than that of TNF-α (p < 0.05).Conclusion: TNF-α enhances the production of a large number of inflammatory factors by cartilage cells, inhibits autophagy of cartilage cells, and promotes cell apoptosis through regulation of NF-κB signaling pathway. Keywords: Icariin, NF-κB signaling pathway, TNF-α, Inflammatory response, Chondrocytes, Autophagy, Apoptosis

Highlights

Osteoarthritis is a chronic degenerative disease which involves the cartilage, subchondral bone and synovium
The purpose of this study was to determine the effect of icariin on TNF-α-mediated inflammatory response, as well as its effect on autophagy and apoptosis of chondrocytes in a rat model of osteoarthritis
The mRNA and protein expressions of ATG5 and ATG7 in the cartilage tissue of rats in the TNF-α intervention group were significantly lower than the corresponding levels in the control group (p < 0.05), but they were significantly higher in the cartilage tissue of rats in the icariin +TNF-α group and NF-κB inhibition +TNF-α group than in

Summary

Introduction

Osteoarthritis is a chronic degenerative disease which involves the cartilage, subchondral bone and synovium. Previous studies have suggested that the pathogenesis of osteoarthritis is associated with joint destruction caused by simple cartilage degeneration. In-depth studies have revealed that inflammatory response plays a very important role in the pathogenesis of osteoarthritis [2]. TNF-α is one of the important inflammatory factors that cause cartilage destruction in osteoarthritis. Studies have shown that TNF-α is distributed in different levels in articular cartilage, subchondral bone and synovium. It promotes the release of fibroblast adhesion molecules and binds to activated vascular endothelial cell adhesion molecules, so that white blood cells in the blood are concentrated in the articular cavity [3]. Chondrocytes are one of the important sources of inflammatory reactions, and they are involved in the synthesis and transformation of extracellular matrix during autophagy and apoptosis [4]

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