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首页> 外文期刊>Journal of Cellular Physiology >Osteoblast differentiation is functionally associated with decreased AMP kinase activity.
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Osteoblast differentiation is functionally associated with decreased AMP kinase activity.

机译：成骨细胞分化功能与AMP激酶活性降低有关。

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Osteoblasts, originating from mesenchymal stem cells, play a pivotal role in bone formation and mineralization. Several transcription factors including runt-related transcription factor 2 (Runx2) have been reported to be essential for osteoblast differentiation, whereas the cytoplasmic signal transduction pathways controlling the differentiation process have not been fully elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis, polarity, and division. Recent lines of evidence have indicated that the activity of the catalytic alpha subunit of AMPK is regulated through its phosphorylation by upstream AMPK kinases (AMPKKs) including LKB1. Here, we explored the role of AMPK in osteoblast differentiation using in vitro culture models. Phosphorylation of AMPKalpha 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 glucose restriction and stimulation with metformin, both of which are known activators of AMPK. Matrix mineralization of MC3T3-E1 cells was also inhibited by the forced expression of a constitutively active form of AMPKalpha. 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.
机译：成骨细胞,来源于间充质干细胞细胞在骨形成和发挥关键作用矿化。包括runt-related转录因子2(Runx2)已报告是必不可少的成骨细胞分化,而胞质信号转导途径控制没有分化过程被完全阐明。激酶(AMPK)是一个serine-threonine激酶通常被认为是一个细胞的主要监管机构能量体内平衡、极性和部门。最近的证据表明,AMPK催化α亚基的活动通过其磷酸化调控上游包括LKB1 AMPK激酶(AMPKKs)。在这里,我们探讨AMPK在成骨细胞的作用利用离体培养模型分化。磷酸化AMPKalpha明显减少在成骨细胞的分化主要造骨细胞和MC3T3-E1,一只老鼠成骨细胞的细胞系。基本成骨细胞和分化MC3T3-E1细胞,由矩阵表示矿化,显著抑制了葡萄糖限制和刺激二甲双胍,这两个的活化剂AMPK。也被强制表达的持续活跃的AMPKalpha形式。二甲双胍显著抑制基因表达Runx2以及成骨细胞的分化标记包括骨钙素(Ocn),骨sialo蛋白(Bsp),骨桥蛋白(Opn)。目前的数据表明,分化成骨细胞功能相关AMPK活性下降。

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