Combined treatment with electrical stimulation and insulin-like growth factor-1 promotes bone regeneration in vitro.

Zhiping Qi,Yuxin Chang,Shuang Zheng,Peng Xia,Chuan Fu,Su Pan,Jincheng Wang,Yue Ma,Xiaoyu Yang,Jung-Eun Kim

doi:10.1371/journal.pone.0197006

Abstract

Electrical stimulation (ES) and insulin-like growth factor-1 (IGF-1) are widely used in bone regeneration because of their osteogenic activity. However, the combined effects of ES and supplemental IGF-1 on the whole bone formation process remain unclear. In this study, fluorescence staining and an MTT assay were first utilized to observe the influence of ES and IGF-1 on MC3T3-E1 cell proliferation and adhesion in vitro. Subsequently, osteogenic differentiation was evaluated by the alkaline phosphatase activity (ALP) and the expression of osteogenic marker genes. In addition, cell mineralization was determined by alizarin red staining and scanning electron microscopy (SEM). We demonstrated that the MC3T3-E1 cell proliferation was significantly higher for treatments combining IGF-1 and ES than for treatments with IGF-1 alone. The combination of IGF-1 and ES increased the MC3T3-E1 cell ALP activity, the expression of osteogenesis-related genes and the calcium deposition with a clear dose-dependent effect. Our data show the synergistic effect of IGF-1 and ES in promoting the proliferation, differentiation and mineralization of MC3T3-E1 cells, which suggests that it would be more effective to combine the proper dose of IGF-1 with ES to promote local bone damage repair and regeneration.

Highlights

Further intervention may end in serious morbidities, such as increased pain and functional limitations, due to nonfulfillment or a slowdown in bone healing[1]
The present study aimed to demonstrate whether insulin-like growth factor-1 (IGF-1) alone or combined with electrical stimulation (ES) was able to regulate the functions of osteogenesis, as well as the appropriate doses
We found that the 200 Hz group had the maximum optical density (OD) value compared to those of the other groups, there were no significant

Summary

Introduction

Further intervention may end in serious morbidities, such as increased pain and functional limitations, due to nonfulfillment or a slowdown in bone healing[1]. The end purpose of the treatment of patients with fractures and surgical osteotomies is a compound physiological process in bone healing. Across a range of symptoms, electrical stimulation (ES) is a widely known adjunctive therapy used to enhance bone healing[2,3,4,5]. A recent randomized shamcontrolled trial to determine the effect of electrical stimulation on bone healing has been performed through meta-analysis. This study found that patients treated with electrical stimulation have significantly less pain and experience lower rates of radiographic nonunion or persistent nonunion[6].

Objectives

Methods

Results

Discussion

Conclusion