Aucubin prevents steroid-induced osteoblast apoptosis by enhancing autophagy via AMPK activation.

Chen Yue,Xue Zhang,Wuyin Li,Youwen Liu,Peijian Tong,Zhen Tan,Deli Wang,Hongting Jin

doi:10.1111/jcmm.16954

Abstract

Steroid‐induced osteoblast apoptosis is a crucial pathological process in steroid‐induced osteonecrosis of the femoral head (SONFH). Autophagy can resist apoptosis and AMPK plays an important role in autophagy regulation. Aucubin from the small tree Eucommia ulmoides Oliv., which has a long history of use in orthopaedics and traumatology in Asian medicine, can promote bone formation, but whether it can slow or prevent steroid‐osteoblast apoptosis is unclear. Therefore, we investigated the pathogenesis of SONFH and how the osteoblast responds to aucubin under the dexamethasone stimulation. In human femoral head osteonecrosis specimens, we found that the autophage and apoptosis level were increased, and the AMPK signalling was crucial to autophagy. We observed that aucubin could prevent dexamethasone‐induced apoptosis in osteoblasts by enhancing the level of autophagy. Further, we confirmed that the regulatory effect of aucubin on autophagy and apoptosis was achieved by activating AMPK signalling. We have demonstrated a mechanism of disease progression and shown that aucubin could enhance autophagy through AMPK signalling to prevent osteoblast apoptosis. These findings provide a basis for the further investigation of the potential therapeutic role of aucubin in the SONFH.

Highlights

As a result of their powerful anti-inflammatory and immunosuppressive ability, steroids such as dexamethasone and prednisone are commonly used to treat systemic lupus erythematosus, nephrotic syndrome and other autoimmune disease.[1,2] excessive steroids usage is a common cause of osteonecrosis of the femoral head.[3]
Recent evidence indicates that autophagy is involved in the regulation of steroid-induced osteoblast apoptosis, which has opened a new avenue of steroid-induced osteonecrosis of the femoral head (SONFH) therapy.[7,8]
Given that the AMP-activated protein kinase (AMPK) signalling pathway can increase autophagy in cells and that p-AMPK levels are increased in human SONFH specimens, we investigated whether aucubin upregulates AMPK signalling to enhance osteoblast autophagy under stimulation by dexamethasone

Summary

| INTRODUCTION

As a result of their powerful anti-inflammatory and immunosuppressive ability, steroids such as dexamethasone and prednisone are commonly used to treat systemic lupus erythematosus, nephrotic syndrome and other autoimmune disease.[1,2] excessive steroids usage is a common cause of osteonecrosis of the femoral head.[3]. Has been widely used to treat many kinds of orthopaedic diseases in Asian countries for thousands of years.[23,24] The iridoid glycoside aucubin (C15H22O9), the principle bioactive component of Eucommia ulmoides Oliv., has been reported to exert several pharmacological effects against inflammation, oxidation and bone loss.23–25 aucubin has recently been shown to prevent apoptosis by regulating the level of autophagy in several disease models.[26,27] little is known about whether and how aucubin might influence steroid-induced autophagy and apoptosis in osteoblast. In this study, we wished to clarify the role of AMPK signalling in disease progression, and to determine whether aucubin could prevent steroid-induced osteoblast apoptosis by modulating autophagy via AMPK activation.

| MATERIALS AND METHODS

| RESULTS

| DISCUSSION

Findings

| CONCLUSION