Roles of AMPK in Osteogenic Differentiation

amp活化蛋白激酶（AMPK）是一种响应机械应力的激酶。在原代成骨细胞和小鼠成骨细胞系MC3T3-E1中，AMPKα的磷酸化水平在成骨细胞分化过程中均显著降低。相反，以基质矿化为代表的原代成骨细胞和MC3T3-E1细胞的终末分化被AMPK激活剂二甲双胍刺激显著抑制。MC3T3-E1细胞的基质矿化也被一种组成型活性AMPKα的强制表达所抑制。二甲双胍显著抑制Runx2基因以及骨钙素（Ocn）、骨钙蛋白（Bsp）和骨桥蛋白（Opn）等成骨细胞分化标志物的表达。因此，我们目前的数据表明，成骨细胞的分化在功能上与AMPK活性降低有关。

AMP-activated protein kinase(AMPK) is a kinase responds to mechanical stress. Phosphorylation of AMPKα was significantly decreased during osteoblastic differentiation in both primary osteoblasts and MC3T3-E1, a mouse osteoblastic cell line. Conversely, the terminal differentiation of primary osteoblasts and MC3T3-E1 cells, represented by matrix mineralization, was significantly inhibited by stimulation with metformin, an activator of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKα Metformin significantly inhibited gene expression of Runx2 along with osteoblast differentiation markers including osteocalcin (Ocn), bone sialo protein (Bsp), and osteopontin (Opn). Thus, our present data indicate that differentiation of osteoblasts is functionally associated with decreased AMPK activity.