Roles of AMPK in Osteogenic Differentiation

AMP活化蛋白激酶（AMPK）是一种对机械应力有反应的激酶。在成骨细胞分化过程中，AMPKα的磷酸化在原代成骨细胞和小鼠成骨细胞系MC 3 T3-E1中均显著降低。相反，原代成骨细胞和MC 3 T3-E1细胞的终末分化（以基质矿化为代表）受到AMPK激活剂二甲双胍刺激的显著抑制。MC 3 T3-E1细胞的基质矿化也受到AMPKα组成型活性形式的强制表达的抑制。Metabolic显著抑制Runx 2的基因表达，沿着成骨细胞分化标志物，包括骨钙素（Ocn）、骨唾液酸蛋白（Bsp）和骨桥蛋白（Opn）。因此，我们目前的数据表明，成骨细胞的分化与AMPK活性降低功能相关。

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.