AMPK 信号通路对骨代谢的调节作用

摘要

Increasing evidence shows that osteoporosis, similar to obesity, could be related to the disorders of energy metabolism. AMP-activated protein kinase ( AMPK) plays an important role in the regulation of cellular energy homeostasis and mediates the effect of many hormones on the metabolisms.Once activated, it switches on catabolic pathways that generate ATP and switches off anabolic pathways that consume ATP.AMPK could be activated not only by adiponectin and leptin secreted by adipocytes, but also by antidiabetic drugs such as metformin and thiazolidinediones.Both adipokines and drugs can affect bone metabolism.Recent findings have also indicated that AMPK signaling pathway plays a role in bone metabolism.Activation of AMPK in vitro can affect osteogenesis.Knocking-out of αorβsubunits of AMPK in mice can lead to the decrease of bone mass and the increase of bone formation and resorption with a negative imbalance.But the mechanism involved in this process remains unclear.This paper reviews the structure and function of AMPK, the role of AMPK in bone tissues, and the relationship between osteogenesis and adipogenesis, and discusses the possibility of AMPK as a new therapeutic target in osteoporosis.%最近越来越多的证据显示骨质疏松症可能与肥胖症类似，也与能量代谢紊乱相关。而腺苷酸活化蛋白激酶（ AMPK）是维持细胞能量平衡以及调节多种代谢相关激素的重要分子，AMPK激活后可以开启分解代谢通路以产生更多的ATP，同时会关闭合成代谢通路以减少ATP的消耗。已知AMPK不仅能被脂肪细胞分泌的脂联素和瘦素激活，还能被抗糖尿病类药物二甲双胍和噻唑烷二酮类激活，而这些脂肪因子和药物都能影响骨代谢，同时最近的研究也表明AMPK信号通路对骨代谢有调节作用。体外激活AMPK可以影响成骨，基因敲除AMPKα或β亚基会使小鼠骨量降低，骨形成和骨吸收同时增加但伴有骨重建的负平衡，但是其中涉及的具体机制并不明确。本文就AMPK的结构和功能、在骨组织细胞中的作用、与成骨成脂分化平衡的关系作一综述，并分析AMPK通路作为骨质疏松症潜在治疗靶点的可能性。