title: BKCa and hEag1 channels regulate cell proliferation and differentiation in human bone marrow-derived mesenchymal stem cells.
abstract: Human bone marrow-derived mesenchymal stem cells (MSCs) serve as a reservoir for the continuous renewal of various mesenchymal tissues; however, cellular physiology of ion channels is not fully understood. The present study investigated potential roles of large-conductance Ca(2+) -activated potassium (BKCa ) channels and ether-à-go-go potassium (hEag1 or Kv10.1) channels in regulating cell proliferation and differentiation in human MSCs. We found that inhibition of BKCa with paxilline or hEag1 with astemizole, or knockdown of BKCa with shRNAs targeting KCa1.1 or hEag1 channels with shRNAs targeting KCNH1 arrested the cells at G0/G1 phase. In addition, silencing BKCa or hEag1 channels significantly reduced adipogenic differentiation with decrease of lipid accumulation and expression of the adipocyte marker PPARγ, and decreased osteogenic differentiation with reduction of mineral precipitation and osteocalcin. These effects were accompanied with a reduced cyclin D1, cyclin E, p-ERK1/2, and p-Akt. Our results demonstrate that BKCa and hEag1 channels not only regulate cell proliferation, but also participate in the adipogenic and osteogenic differentiations in human MSCs, which indicates that BKCa and hEag1 channels may be essential in maintaining bone marrow physiological function and bone regeneration.
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yue
authors.forename: Hui
authors.initials: H
authors.lastname: Che
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D007211:Indoles; C496884:KCNH1 protein, human; C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C048220:paxilline