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，ampk α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基因及成骨细胞分化标志物的表达。临床上用于促进骨折愈合的低强度脉冲超声（LIPUS）可降低ampk α的磷酸化。因此，LIPUS可能通过AMPK的去磷酸化促进成骨细胞分化。

AMP-activated protein kinase(AMPK) is a kinase responds to mechanical stress. Phosphorylation of AMPKαwas 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. Low-intensity pulsed ultrasound (LIPUS), which is used clinically to promote bone fracture healing, decreased AMPKαphosphorylation. Thus, LIPUS may promote osteoblast differentiation through dephosphorylation of AMPK.