Osteoblast AMP-activated protein kinase regulates glucose metabolism and bone mass in adult mice
Osteoblast AMP-activated protein kinase regulates glucose metabolism and bone mass in adult mice
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DOI：
10.1016/j.bbrc.2018.07.141
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发表时间：
2018-09-10
影响因子：
3.1
通讯作者：
Sugimoto, Toshitsugu
中科院分区：
文献类型：
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作者：
Kanazawa, Ippei;Takeno, Ayumu;Sugimoto, Toshitsugu
以往的研究表明，AMP激活的蛋白激酶(AMPK)是能量稳态的重要调节因子，在成骨细胞的分化和矿化过程中发挥着重要作用。然而，成骨细胞AMPK在成年小鼠体内对糖代谢和骨量调节的作用知之甚少。在这里，我们使用了可诱导的Cre系统，通过取消补充多西环素来控制出生后AMPK中断的发生。我们有条件地灭活了3周龄AMPK(-/-)小鼠的Osterix(OSX)表达细胞中的AMPK。AMPK失活6个月后，与野生型小鼠相比，AMPK(-/-)小鼠的血清骨钙素水平以及葡萄糖耐量试验和胰岛素耐受试验分别显示出较低的血清骨钙素水平以及葡萄糖耐量和胰岛素抵抗。AMPK失活18个月后，微型计算机断层扫描显示，与野生型小鼠相比，AMPK(-/-)小鼠股骨的骨小梁体积和皮质骨厚度显著减少。此外，AMPK(-/-)小鼠的骨硬度明显低于野生型小鼠。这是第一次研究表明成骨细胞AMPK在葡萄糖代谢和维持成年小鼠的骨小梁体积、皮质厚度和骨强度方面发挥重要作用。(C)2018 Elsevier Inc.保留所有权利。
Previous studies have shown that AMP-activated protein kinase (AMPK), a crucial regulator of energy homeostasis, plays important roles in osteoblast differentiation and mineralization. However, little is known about in vivo roles of osteoblastic AMPK in glucose metabolism and bone mass regulation in adult mice. Here, we used the inducible Cre system to control the onset of Ampk disruption after birth by removing doxycycline supplementation. We conditionally inactivated Ampk in osterix (Osx)-expressing cells in 3-week-old Ampk(-/-) mice. After 6 months of Ampk inactivation, the Ampk(-/-) mice displayed lower serum osteocalcin levels as well as glucose intolerance and insulin resistance, as indicated by glucose tolerance and insulin tolerance tests, respectively, when compared with wild-type mice. After 18 months of Ampk inactivation, micro computed tomography showed significant reductions in trabecular bone volume and cortical bone thickness in the femur of Ampk(-/-) mice when compared with wild-type mice. Moreover, bone stiffness was significantly lower in Ampk(-/-) mice than in wild-type mice. This is the first study to show that osteoblast AMPK plays an important roles in glucose metabolism and in maintaining trabecular bone volume, cortical thickness, and bone strength in adult mice. (C) 2018 Elsevier Inc. All rights reserved.