BK ablation attenuates osteoblast bone formation via integrin pathway
BK ablation attenuates osteoblast bone formation via integrin pathway
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BK 消融通过整合素途径减弱成骨细胞骨形成
DOI：
10.1038/s41419-019-1972-8
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发表时间：
2019-09
影响因子：
9
通讯作者：
Xuemei Zhang
中科院分区：
文献类型：
--
作者：
Yinhang Wang;Qiang Guo;Hongya Hei;Jie Tao;Yi Zhou;Jibin Dong;Hong Xin;Hui Cai;Jianjun Gao;Ker Yu;Svetlana Reilly;Peihao Yin;Xuemei Zhang
骨形成受损是骨质疏松症中发生的低骨量和骨骼脆性的主要原因之一。然而，骨形成缺陷的机制还不清楚。在这里，我们报告，大电导钙激活钾通道（BK）所需的骨形成和成骨细胞功能在体内和体外。到15周龄时，BK敲除（BKO）小鼠表现出胫骨和腰椎的骨矿物质密度和骨小梁体积的下降，这与骨形成和成骨细胞活性受损有关。从机制上讲，BKO小鼠的骨和骨髓间充质干细胞（BMSC）中的BK消融抑制了整合素信号传导。进一步证实了BK α亚基与成骨细胞中整合素β1蛋白的结合，并证实了ROS 17/2. 8成骨细胞中BK α亚基编码蛋白KCNMA 1的基因修饰参与了FAK-ERK 1/2信号转导。这些发现表明BK通过整合素途径促进成骨细胞分化来调节骨形成，这为成骨细胞调节中离子转运蛋白与细胞外基质的串扰提供了新的见解，并揭示了一种新的潜在干预策略，以纠正骨形成缺陷。
Impaired bone formation is one of the major causes of low bone mass and skeletal fragility that occurs in osteoporosis. However, the mechanisms underlying the defects in bone formation are not well understood. Here, we report that big conductance calcium-activated potassium channels (BKs) are required for bone formation and osteoblast function both in vivo and in vitro. By 15 weeks of age, BK knockout (BKO) mice exhibited a decline in bone mineral density and trabecular bone volume of the tibiae and lumbar vertebrae, which were associated with impaired bone formation and osteoblast activity. Mechanistically, BK ablation in bone and bone marrow mesenchymal stem cells (BMSCs) of BKO mice inhibited integrin signaling. Furthermore, the binding of α subunit of BK with integrin β1 protein in osteoblasts was confirmed, and FAK-ERK1/2 signaling was proved to be involved by genetic modification of KCNMA1 (which encodes the α subunit of BK) in ROS17/2.8 osteoblast cells. These findings indicated that BK regulates bone formation by promoting osteoblast differentiation via integrin pathway, which provided novel insight into ion transporter crosstalk with the extracellular matrix in osteoblast regulation and revealed a new potential strategy for intervention in correcting bone formation defects.
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影响因子：
3.5
作者：
MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.9
作者：
S. Korn;Josef G. Trapani
通讯作者：
S. Korn;Josef G. Trapani
DOI：
10.1074/jbc.m112.346171
发表时间：
2012-05
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
N. Savalli;A. Pantazis;T. Yusifov;D. Sigg;R. Olcese
通讯作者：
N. Savalli;A. Pantazis;T. Yusifov;D. Sigg;R. Olcese
DOI：
10.1007/978-1-59745-526-8
发表时间：
2009
期刊：
--
影响因子：
--
作者：
John M. Walker
通讯作者：
John M. Walker
影响因子：
5.6
作者：
Ying-ying Zhang;J. Yue;H. Che;Hai-ying Sun;H. Tse;Gui-Rong Li
通讯作者：
Ying-ying Zhang;J. Yue;H. Che;Hai-ying Sun;H. Tse;Gui-Rong Li