BKCa and hEag1 Channels Regulate Cell Proliferation and Differentiation in Human Bone Marrow‐Derived Mesenchymal Stem Cells
BKCa and hEag1 Channels Regulate Cell Proliferation and Differentiation in Human Bone Marrow‐Derived Mesenchymal Stem Cells
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DOI：
10.1002/jcp.24435
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发表时间：
2014-02
影响因子：
5.6
通讯作者：
Ying-ying Zhang;J. Yue;H. Che;Hai-ying Sun;H. Tse;Gui-Rong Li
中科院分区：
文献类型：
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作者：
Ying-ying Zhang;J. Yue;H. Che;Hai-ying Sun;H. Tse;Gui-Rong Li
人骨髓来源的间充质干细胞（MSCs）是各种间充质组织持续更新的储存库；然而，离子通道的细胞生理学尚不完全清楚。本研究调查了大电导Ca2+活化钾（BKCa）通道和醚- <s:1> - go - go钾（hEag1或Kv10.1）通道在调节人间充质干细胞细胞增殖和分化中的潜在作用。我们发现，用paxilline抑制BKCa或用阿司咪唑抑制hEag1，或用靶向KCa1.1的shrna抑制BKCa，或用靶向KCNH1的shrna抑制hEag1通道，使细胞在G0/G1期停滞。此外，沉默BKCa或hEag1通道可显著降低成脂分化，减少脂质积累和脂肪细胞标记物PPARγ的表达，并通过减少矿物沉淀和骨钙素来降低成骨分化。这些影响伴随着细胞周期蛋白D1、细胞周期蛋白E、p - ERK1/2和p - Akt的降低。我们的研究结果表明，BKCa和hEag1通道不仅调节细胞增殖，还参与人间充质干细胞的成脂和成骨分化，这表明BKCa和hEag1通道可能在维持骨髓生理功能和骨再生中至关重要。j .细胞。中国生物医学工程学报，2014,32(2):557 - 557。©2013 Wiley期刊公司
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 Ca2+‐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. J. Cell. Physiol. 229: 202–212, 2014. © 2013 Wiley Periodicals, Inc.