Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

Yini Jiang,Danni Sun,Weiheng Chen,Xiaomin Li,Ying Xu,Chunfang Liu,Na Lin,Xia Mao,Qiuyan Guo,Yanqiong Zhang,Zhenli Liu

doi:10.1186/s12967-014-0334-7

Abstract

BackgroundSteroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms.MethodsSteroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels.ResultsThe ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro.ConclusionABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

Highlights

Steroid-induced osteonecrosis of the femoral head presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation
Compared with the control group, there was an accumulation of bone marrow cell debris found in ONFH lesions in the model group, while Achyranthes bidentata extract (ABE) treatment dramatically attenuated this change in rats with steroid-induced ONFH (Figure 2A)
The adipose tissue area and adipocyte perimeter in the bone marrow, which were dramatically increased in rats with steroid-induced ONFH, were dose-dependently reduced by ABE treatment (Figure 2B)

Summary

Introduction

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. Owing to the various effects of steroids on multi-system pathways involved in osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism, and coagulation, it has been challenging to fully elucidate the pathogenesis and etiology of steroid-induced ONFH [3]. Current treatment for steroid-induced ONFH focuses on preventing irreversible complications, such as biomechanical collapse of the femoral head and osteoarthritis of the hip joint. These treatments were limited in their ability to enhance bone repair and to prevent collapse of the articular surface and hip arthroplasty [5]. Novel and efficient agents for the treatment of this disease are needed

Objectives

Methods

Results

Conclusion