β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

Abstract

Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). β-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that β-ecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that β-ecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of β-ecdysterone on IDD was explored by in vitro experiments. The results demonstrated that β-ecdysterone attenuated the apoptosis induced by tert-butyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin-1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by β-ecdysterone in a dose-and time-dependent manner in nucleus pulposus cells. Inhibition of autophagy with 3-methyladenine partially abrogated the protective function of β-ecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of β-ecdysterone on IDD. Additionally, β-ecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that β-ecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that β-ecdysterone may be a potential therapeutic agent for IDD.

Regulation of osteoblast autophagy based on PI3K/AKT/mTOR signaling pathway study on the effect of β-ecdysterone on fracture healing

“…On the contrast, the osteogenic differentiation in osteoblasts and the fracture healing of fracture rats were dramatically repressed by the autophagy inhibitor 3-methyladenine, which further identified the involvement of autophagy in the repair of fracture healing. As verified in the present study, similar to rapamycin, β-ecdysterone was found to be an agonist of autophagy, which was consistent with the research by Wen et al [17] in 2019 and Tang et al [11] in 2020. Interestingly, the activation of autophagy induced by β-ecdysterone was accompanied by facilitated osteogenic differentiation in osteoblasts and the fracture healing, indicating that the effects of β-ecdysterone on fracture healing might be related to the activation of autophagy in osteoblasts.…”

An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms

“…Ecdy can promote autophagy upon the onset of osteoporosis in rats (Tang et al, 2018). In addition, Ecdy protects from degeneration human nucleus pulposus cells, which form the inner core of the vertebral disc (Wen et al, 2019). This effect is mediated by Ecdy-dependent induction of autophagy, which counteracts the effect of apoptosis.…”

Relationships Between Disc Degeneration and Autophagy Expression in Human Nucleus Pulposus

“…Studies have shown that autophagy plays an important protective role in the cell catabolic pathway, leading to lysosomal degradation in aging‐related and degenerative diseases. Wen et al (2019) reported that β‐ecdysterone protects disc nucleus pulposus against apoptosis through autophagy activation and ameliorates IDD. Ye et al proposed that autophagy was present and associated with increased pathological IDD in rats.…”