Nanosecond pulsed electric fields (nsPEFs) regulate phenotypes of chondrocytes through Wnt/β-catenin signaling pathway.

Kun Zhang,Jinsong Guo,Zigang Ge,Jue Zhang

doi:10.1038/srep05836

Abstract

Nanosecond pulsed electric fields (nsPEFs) characterized by high voltage, low energy and non-thermal effects, have been broadly investigated as a potential tumor therapy; however, little is known about their effects on somatic cells. In this current study, we evaluated effects of nsPEFs on the phenotype of chondrocytes (morphology, glycosaminoglycan (GAG) content, proliferation and gene expression) and explored the mechanisms involved. Our results demonstrated that exposing chondrocytes to nsPEFs led to enhanced proliferation and dedifferentiation, evidenced by the upregulated gene expression of collagen type I (COL I) and downregulated gene expression of Sox9, collagen type II (COL II) and aggrecan (AGG) with activation of the wnt/β-catenin signaling pathway. Inhibition of the wnt/β-catenin pathway partially blocked these effects. Thus we concluded that nsPEFs induce dedifferentiation of chondrocytes partially through transient activation of the wnt/β-catenin signaling pathway.

Highlights

Nanosecond pulsed electric fields characterized by high voltage, low energy and non-thermal effects, have been broadly investigated as a potential tumor therapy; little is known about their effects on somatic cells
Our results demonstrated that exposing chondrocytes to Nanosecond pulsed electric fields (nsPEFs) led to enhanced proliferation and dedifferentiation, evidenced by the upregulated gene expression of collagen type I (COL I) and downregulated gene expression of Sox[9], collagen type II (COL II) and aggrecan (AGG) with activation of the wnt/b-catenin signaling pathway
Exposing chondrocytes to nsPEFs at 10 kV/cm increased absorbance values obtained from MTT assay to 1.07-fold, 1.05-fold and 1.05-fold, while nsPEFs at 20 kV/cm caused a 1.24-fold (p 5 0.002), 1.04-fold and 1.16-fold (p 5 0.018) increase at days 1, 3 and 7, respectively (Fig. 2a). nsPEFs appeared to have no significant effect on chondrocyte morphology (Supplementary Fig. S1). nsPEFs at 10 kV/cm revealed a slight increase in proliferation of chondrocytes at day 1 (1.14-fold), day 3 (1.03-fold) and day 7 (1.06-fold), whereas nsPEFs at 20 kV/cm significantly increased cell proliferation at day 1 (1.21-fold, p 5 0.02), day 3 (1.18-fold, p 5 0.02) and day 7 (1.04-fold) (Fig. 2b)

Summary

Introduction

Nanosecond pulsed electric fields (nsPEFs) characterized by high voltage, low energy and non-thermal effects, have been broadly investigated as a potential tumor therapy; little is known about their effects on somatic cells. In this current study, we evaluated effects of nsPEFs on the phenotype of chondrocytes (morphology, glycosaminoglycan (GAG) content, proliferation and gene expression) and explored the mechanisms involved. Nanosecond pulsed electric fields (nsPEFs) have shown some advantages over millisecond or microsecond PEFs, as they can achieve similar membrane potentials with higher voltage differentials, lower energy and negligible thermal effects. We explored whether activation of the wnt/b-catenin signaling pathway was involved in these phenotypic changes (Fig. 1)

Methods

Results

Conclusion