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首页> 外文期刊>Redox Biology >Mechanically induced autophagy is associated with ATP metabolism and cellular viability in osteocytes in vitro
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Mechanically induced autophagy is associated with ATP metabolism and cellular viability in osteocytes in vitro

机译：机械诱导的自噬与骨细胞体外的ATP代谢和细胞活力有关

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Both mechanical loading and intracellular autophagy play important roles in bone homeostasis; however, their relationship remains largely unexplored. The objectives of this study were to determine whether osteocytes undergo autophagy upon fluid shear stress (FSS) loading and to determine the correlation between mechanically induced autophagy and ATP metabolism. Autophagic vacuoles were observed by transmission electron microscopy (TEM) in osteocyte-like MLO-Y4 cells subjected to FSS. Increased autophagic flux was further confirmed by the increased amount of the LC3-II isoform and the degradation of p62. Fluorescent puncta distributed in the cytoplasm were observed in the GFP-LC3 transformed cells subjected to FSS. Furthermore, FSS-induced ATP release and synthesis in osteocytes were attenuated by inhibiting autophagy with 3-MA. After FSS exposure, a high ratio of cell death was observed in cultures pretreated with 3-MA, an autophagy inhibitor, with no significantly different Caspase 3/7 activity. Our results indicated that FSS induces protective autophagy in osteocytes and that mechanically induced autophagy is associated with ATP metabolism and osteocyte survival. From the clinical perspective, it may be possible to enhance skeletal cell survival with drugs that modulate the autophagic state, and the autophagy-related pathway could be a potential target for the prevention of ageing-related bone disorders.
机译：机械负荷和细胞内自噬在骨稳态中都起着重要作用。但是，他们之间的关系在很大程度上尚未得到探索。这项研究的目的是确定骨细胞是否在流体剪切应力（FSS）负荷下经历自噬，并确定机械诱导的自噬与ATP代谢之间的相关性。通过透射电子显微镜（TEM）在经历FSS的骨细胞样MLO-Y4细胞中观察到自噬泡。 LC3-II同工型的增加和p62的降解进一步证实了自噬通量的增加。在经历FSS的GFP-LC3转化细胞中观察到分布在细胞质中的荧光点。此外，FSS诱导的骨细胞中ATP释放和合成被3-MA抑制自噬而减弱。在FSS暴露后，在用自噬抑制剂3-MA预处理的培养物中观察到高比例的细胞死亡，而Caspase 3/7活性没有显着差异。我们的结果表明，FSS诱导骨细胞保护性自噬，而机械诱导的自噬与ATP代谢和骨细胞存活相关。从临床的角度来看，用调节自噬状态的药物可以增强骨骼细胞的存活，并且自噬相关的途径可能是预防与衰老有关的骨病的潜在靶标。

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