Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Cells Tissues Organs. 2011;194(2-4):274-8. doi: 10.1159/000324647. Epub 2011 May 19.
The goal of this investigation was to ascertain whether bone cells undergo autophagy and to determine if this process is regulated by environmental factors. We showed that osteocytes in both murine and human cortical bone display a punctuate distribution of microtubule-associated protein light chain 3, indicative of autophagy. In addition, we noted a basal level of autophagy in preosteocyte-like murine long bone-derived osteocytic (MLO)-A5 cells. Autophagy was upregulated following nutrient deprivation and hypoxic culture, stress conditions that osteocytes encounter in vivo. Furthermore, in response to calcium stress, the transcription factor hypoxia inducible factor 1 regulated MLO-A5 autophagy. Finally, we showed that the more differentiated MLO-Y4 osteocyte-like cells exhibited a significant basal autophagic flux. Based on these findings, we suggest that raising the level of autophagic flux is a mechanism by which differentiated bone cells survive in a stressful environment.
本研究旨在确定骨细胞是否会发生自噬，并确定该过程是否受到环境因素的调节。我们表明，在鼠和人皮质骨中的骨细胞中，微管相关蛋白轻链 3 呈点状分布，表明存在自噬现象。此外，我们还观察到类成骨细胞样鼠长骨来源的骨细胞（MLO）-A5 细胞中存在基础水平的自噬。自噬在营养剥夺和缺氧培养后被上调，这是骨细胞在体内遇到的应激条件。此外，在钙应激下，转录因子缺氧诱导因子 1 调节 MLO-A5 自噬。最后，我们表明，分化程度更高的 MLO-Y4 类骨细胞样细胞表现出明显的基础自噬通量。基于这些发现，我们认为提高自噬通量的水平是分化的骨细胞在应激环境中存活的一种机制。
