title: KCNK1 inhibits osteoclastogenesis by blocking the Ca2+ oscillation and JNK-NFATc1 signaling axis.
abstract: KCNK1 (K(+) channel, subfamily K, member 1) is a member of the inwardly rectifying K(+) channel family, which drives the membrane potential towards the K(+) balance potential. Here, we investigated its functional relevance during osteoclast differentiation. KCNK1 was significantly induced during osteoclast differentiation, but its functional overexpression significantly inhibited osteoclast differentiation induced by RANKL (also known as TNFSF11), which was accompanied by the attenuation of the RANKL-induced Ca(2+) oscillation, JNK activation and NFATc1 expression. In contrast, KCNK1 knockdown enhanced the RANKL-induced osteoclast differentiation, JNK activation and NFATc1 expression. In conclusion, we suggest that KCNK1 is a negative regulator of osteoclast differentiation; the increase of K(+) influx by its functional blockade might inhibit osteoclast differentiation by inhibiting Ca(2+) oscillation and the JNK-NFATc1 signaling axis. Together with the increased attention on the pharmacological possibilities of using channel inhibition in the treatment of osteoclast-related disorders, further understanding of the functional roles and mechanisms of K(+) channels underlying osteoclast-related diseases could be helpful in developing relevant therapeutic strategies.
authors.affiliation: Research Institute of Basic Science, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Chun
authors.affiliation: Department of Oral Physiology, College of Dentistry, Institute of Wonkwang Biomaterial and Implant, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Hae In
authors.initials: HI
authors.lastname: Lee
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon 540-742, Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea hwan@krict.re.kr superwon@krict.re.kr.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea hwan@krict.re.kr superwon@krict.re.kr.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: C486372:Kcnk1 protein, mouse; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D024683:Potassium Channels, Tandem Pore Domain; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse
keywords: Ca2+; JNK; K+ channel; KCNK1; NFATc1; Osteoclast