Effect of risperidone on proliferation and apoptosis of MC3T3-E1 cells.

Lei Zheng,Yiming Wang,Niya Long,Lixia Yang,Peifan Li,Xin Zhao

doi:10.1590/1414-431x20188098

Abstract

This aim of this study was to assess the molecular mechanism of osteoporosis in schizophrenia patients with risperidone use. Here, we investigated the effects of risperidone on cellular proliferation and apoptosis of a preosteoblast cell line, MC3T3-E1. Cell viability and apoptotic rate of MC3T3-E1 were detected by cell counting kit-8 and flow cytometry at a serial dose of risperidone and at different time points, respectively. Bone transformation relevant gene serum osteocalcin (BGP), collagen 1, tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) mRNA levels were determined by real-time PCR (qPCR). Their protein expression patterns were evaluated using western blot. The results revealed that risperidone dramatically inhibited MC3T3-E1 cell proliferation in a dose-dependent manner. It also significantly induced MC3T3-E1 cell apoptosis. TNF-α gene and protein levels were greatly enhanced after risperidone treatment. In contrast, BGP, collagen 1, OPG, and RANKL gene and protein levels were markedly downregulated. Our study indicated that risperidone suppressed MC3T3-E1 cell proliferation and induced apoptosis. It also regulated BGP gene and protein expression.

Highlights

Schizophrenia is one of the most common mental disorders characterized by severe abnormal behavior and chronic relapsing [1]
In contrast to 24-h (Figure 1A) and 72-h (Figure 1C) culture, the maximal suppressing effects were achieved at 48-h (Figure 1B) culture. This experiment revealed that risperidone suppressed preosteoblast cell proliferation in a dose-dependent manner
The apoptotic rate of 100 mmol/L risperidone-treated cells was markedly higher than that of 50 mmol/L-treated cells (Figure 2D, Po0.05). These data demonstrated that risperidone can cause MC3T3-E1 cell apoptosis in a dose-dependent manner

Summary

Introduction

Schizophrenia is one of the most common mental disorders characterized by severe abnormal behavior and chronic relapsing [1]. Patients take drugs for controlling symptoms for long terms. Risperidone is one of the atypical antipsychotics for the most severe schizophrenia patients because of its excellent effects. Studies show that patients receiving risperidone for a long time have increased risk of osteoporosis [2,3]. The rate of femoral neck fracture in patients taking risperidone is more than two-fold that of the normal population, and it may cause the death of patients [4,5]. The mechanism of osteoporosis in schizophrenia patients taking risperidone is unclear. Elucidating this mechanism may enhance the drug’s safety and patient life quality

Methods

Results

Conclusion