ß­ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration.

Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). ß-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that ß­ecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that ß­ecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of ß­ecdysterone on IDD was explored by in vitro experiments. The results demonstrated that ß­ecdysterone attenuated the apoptosis induced by tert­butyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin­1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by ß­ecdysterone in a dose­ and time­dependent manner in nucleus pulposus cells. Inhibition of autophagy with 3­methyladenine partially abrogated the protective function of ß­ecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of ß­ecdysterone on IDD. Additionally, ß­ecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that ß­ecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that ß­ecdysterone may be a potential therapeutic agent for IDD.