title: The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization.
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.
authors.affiliation: 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. didwldms@snu.ac.kr.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Yang
authors.affiliation: 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. gan14@snu.ac.kr.
authors.forename: Min Seok
authors.initials: MS
authors.lastname: Song
authors.affiliation: 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. sym1987@snu.ac.kr.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shen
authors.affiliation: 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. pdryu@snu.ac.kr.
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
authors.affiliation: 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. leeso@snu.ac.kr.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051659:KCNQ3 Potassium Channel / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D026902:Potassium Channel Blockers / Q000494:pharmacology; D000076182:Sp7 Transcription Factor; D016704:Synapsins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D051659:KCNQ3 Potassium Channel; D026902:Potassium Channel Blockers; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D016704:Synapsins; D014157:Transcription Factors; D015675:Osteocalcin; D018698:Glutamic Acid; D000469:Alkaline Phosphatase
keywords: KCNQ channels; differentiation; glutamate; matrix mineralization