AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells
AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells
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DOI：
10.1016/j.bbrc.2010.12.099
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发表时间：
2011-01-28
影响因子：
3.1
通讯作者：
Koh, Jeong-Tae
中科院分区：
文献类型：
--
作者：
Jang, Won Gu;Kim, Eun Jung;Koh, Jeong-Tae
本研究探讨了 AMPK 激活在成骨细胞分化中的作用及其潜在机制。 AMPK 激活剂（AICAR 或二甲双胍）刺激成骨细胞分化，增加 ALP 和 OC 蛋白的产生，并诱导 MC3T3E1 细胞中的 AMPK 磷酸化。此外，二甲双胍诱导 Smad1/5/8 磷酸化以及 Dlx5 和 Runx2 表达，而化合物 C 或显性失活 AMPK 抑制这些作用。瞬时转染研究还表明，二甲双胍增加了 BRE-Luc 和 Runx2-Luc 活性，而这些活性可被 DN-AMPK 或化合物 C 抑制。siRNA 下调 Dlx5 表达可抑制二甲双胍诱导的 Runx2 表达。这些结果表明AMPK的激活通过调节Smad1/5/8-Dlx5-Runx2信号通路刺激成骨细胞分化。 Crown 版权所有 (C) 2010 由 Elsevier Inc. 出版。保留所有权利。
This study examined the role of AMPK activation in osteoblast differentiation and the underlining mechanism. An AMPK activator (AICAR or metformin) stimulated osteoblast differentiation with increases in ALP and OC protein production as well as the induction of AMPK phosphorylation in MC3T3E1 cells. In addition, metformin induced the phosphorylation of Smad1/5/8 and expression of Dlx5 and Runx2, whereas compound C or dominant negative AMPK inhibited these effects. Transient transfection studies also showed that metformin increased the BRE-Luc and Runx2-Luc activities, which were inhibited by DN-AMPK or compound C. Down-regulation of Dlx5 expression by siRNA suppressed metformin-induced Runx2 expression. These results suggest that the activation of AMPK stimulates osteoblast differentiation via the regulation of Smad1/5/8-Dlx5-Runx2 signaling pathway. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.