Nanosecond Pulsed Electric Fields (nsPEFs) Regulate Phenotypes of Chondrocytes through Wnt/β-catenin Signaling Pathway

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.

Diverse effects of pulsed electrical stimulation on cells - with a focus on chondrocytes and cartilage regeneration

“…PES activates MAPK signaling pathway. PES not only upregulates phosphorylation of ERK and p38 (Zhao et al, 2006), but can also activate JNK, another member of the MAPK family, with fast increased phosphorylation level within minutes, which then decreases within 1 h (Morotomi-Yano et al, 2011a;2011b). As the signaling pathways activated by PES may become inactivated within minutes or hours, the effect caused by PES may last for minutes, hours, or days.…”

Effects of electrical stimulation on cell activity, cell cycle, cell apoptosis and β‑catenin pathway in the injured dorsal root ganglion cell

“…Studies of neurodegenerative diseases have demonstrated that the Wnt/β-catenin signaling pathway regulates the proliferation and differentiation of neural stem cells and their precursor cells in the spinal cord (16,17). in addition, animal models of spinal cord injury have indicated that ES influences the proliferation and directional migration of nerve cells via the Wnt/β-catenin signaling pathway (18)(19)(20). In the field of oncology, it has been demonstrated that inhibition of the Wnt signaling pathway can lead to inhibition of cell proliferation and cell cycle, as well as the expression levels of β-catenin, which are associated with the activation and shutdown of Wnt signaling that regulates expression levels of downstream target genes, such as cyclin d1, c-myc, e-cadherin and lgr5, at the transcriptional level, thereby influencing the progression of tumors (21)(22)(23)(24)(25).…”

The effect of electric fields on hyaline cartilage: an in vitro and in silico study

“…Similar to EFs, electromagnetic fields (EMFs) have been applied in in vivo and in vitro studies using cartilage and growth plate explants, and tridimensional structures (Table 4-2) [151], [152], [154], [165], [170], [172], [184]. Similar to EFs, the technique of deliver EMFs consists of an indirect coupling system that uses external parallel coils connected to a function generator (Figure 4-1B) [152], [153], [163], [184].…”

“…The application of EMFs in monolayer cultures have shown preservation of chondrocytes morphology [153], increased DNA synthesis [160], and enhancement of proliferation and GAGs synthesis in human chondrocytes [192]. It has also been demonstrated that EMFs significantly increase cell population but decrease the synthesis of characteristic molecules of hyaline cartilage such as collagen type II, aggrecan, SOX-9, and GAGs [154].…”

“…In turn, overweight or strong impact loading have been proven to cause damage in the ECM and chondrocyte apoptosis, resulting in dysfunction of the tissue and subsequent damage [1], [45], [52], [146]. Several studies have shown that hyaline cartilage behavior is also affected by electrical and electromagnetic stimuli, resulting in changes in cell dynamics, such as migration [147], differentiation [148]- [150], morphology [151]- [154], proliferation [155]- [160], and gene expression [161]- [174]. This implies that mechanical, electrical, and electromagnetic stimulation may have an important role in the regulation of hyaline cartilage in both normal and pathological conditions.…”