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Int. J. Mol. Sci. 2016, 17(3), 407;

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

Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea
Author to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 2 March 2016 / Revised: 2 March 2016 / Accepted: 10 March 2016 / Published: 18 March 2016
(This article belongs to the Section Biochemistry)
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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. View Full-Text
Keywords: KCNQ channels; differentiation; matrix mineralization; glutamate KCNQ channels; differentiation; matrix mineralization; glutamate

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Yang, J.E.; Song, M.S.; Shen, Y.; Ryu, P.D.; Lee, S.Y. The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization. Int. J. Mol. Sci. 2016, 17, 407.

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