The Role of K(V)7.3 in Regulating Osteoblast Maturation and Mineralization

KCNQ (K(V)7) channels are voltage-gated potassium (K(V)) channels, and the function of K(V)7 channels in muscles, neurons, and sensory cells is well established. We confirmed that overall blockade of K(V) channels with tetraethylammonium augmented the mineralization of bone-marrow-derived human mesenchymal stem cells during osteogenic differentiation, and we determined that K(V)7.3 was expressed in MG-63 and Saos-2 cells at the mRNA and protein levels. In addition, functional K(V)7 currents were detected in MG-63 cells. Inhibition of K(V)7.3 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 K(V)7.3 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 K(V)7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that K(V)7.3 could be a novel regulator in osteoblast differentiation.