The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization.

Ji Yang,Min Song,So Lee,Pan Ryu,Yiming Shen

doi:10.3390/ijms17030407

Ji Yang, Min Song + Show 3 more

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https://doi.org/10.3390/ijms17030407

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Abstract

KCNQ (KV7) channels are voltage-gated potassium (KV) channels, and the function of KV7 channels in muscles, neurons, and sensory cells is well established. We confirmed that overall blockade of KV channels with tetraethylammonium augmented the mineralization of bone-marrow-derived human mesenchymal stem cells during osteogenic differentiation, and we determined that KV7.3 was expressed in MG-63 and Saos-2 cells at the mRNA and protein levels. In addition, functional KV7 currents were detected in MG-63 cells. Inhibition of KV7.3 by linopirdine or XE991 increased the matrix mineralization during osteoblast differentiation. This was confirmed by alkaline phosphatase, osteocalcin, and osterix in MG-63 cells, whereas the expression of Runx2 showed no significant change. The extracellular glutamate secreted by osteoblasts was also measured to investigate its effect on MG-63 osteoblast differentiation. Blockade of KV7.3 promoted the release of glutamate via the phosphorylation of extracellular signal-regulated kinase 1/2-mediated upregulation of synapsin, and induced the deposition of type 1 collagen. However, activation of KV7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that KV7.3 could be a novel regulator in osteoblast differentiation.

Highlights

Voltage-gated K+ (KV) channels are one of the largest gene families among the K+ channel groups
We identified that KV7.3 inhibition using linopirdine or XE991 increased mineralization during osteoblast differentiation
Due to the fact that KV7 channels are sensitive to TEA [36,75] and there is a relationship between the M-current of KV7 channels and Ca2+ [30,48,49,50,51,52], a key factor of bone homeostasis, we examined the effect of KV7 channels on osteoblast differentiation by conducting MG-63 and Saos-2 osteoblast-like cells

Summary

Introduction

Voltage-gated K+ (KV) channels are one of the largest gene families among the K+ channel groups. KV channels are known for regulating cellular electrophysiological properties in excitable cells such as neurons [1,2,3] and muscle cells [4,5,6]. In neurons and cardiac muscle cells, KV channels repolarize the cell membrane after the action potential; in association with this action, KV channels modulate the firing rate of the action potential, membrane stabilization, and neurotransmission [7,8]. KV channels may affect cell volume [13,28] and cell signaling [29], leading to diverse cellular activities

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