Autophagy is an evolutionarily conserved dynamic process and present in variety of cells at basal levels to maintain homeostasis and to promote cell survival in response to stresses. The early bone loss with excessive glucocorticoids (GCs) was reported to be related with the extension of the life span of osteoclasts. However, the connection between GCs induced bone loss and osteoclast autophagy remains to be elucidated. Autophagy was detected in a Dexamethasone (Dex) induced osteoporotic mice model and primary osteoclast cultures by autophagosome detection kit, and autophagy-related proteins were assayed by Western blotting and Immunostaining. The bone morphology was examined by micro-CT and TRAP staining. The trabecular bone micro-architecture was deteriorated, and the osteoclast number and spread area were increased in the Dex-treated mice compared with the control group (P < 0.01). Meanwhile, autophagy in pre-osteoclasts was increased in mice under Dex administration evidenced by the increased number of autophagosome and up-regulation of autophagy-related protein levels. Further, the enhanced autophagy under Dex treatment was verified in primary cultured osteoclasts, as shown by the increased levels of Beclin 1 and LC3-II/LC3-I and the autophagy complex formation members including Atg1, Atg13, and Atg7. However, the expressions of PI3K, p-Akt and p-mTOR in primary cultured osteoclasts were inhibited under Dex induced autophagy. Using the selective PTEN inhibitor SF1670 to activate the PI3K/Akt/mTOR pathway reversed this osteoclast autophagy under Dex treatment. Our study suggests that osteoclast autophagy was enhanced in glucocorticoids induced bone loss, and the PI3K/Akt/mTOR signaling pathway mediated the increased autophagy in primary cultured osteoclasts under glucocorticoids treatment.

自噬是一种进化保守的动态过程，在基础细胞中存在于各种细胞中，以维持体内稳态并促进细胞在压力下的存活。据报道，过量糖皮质激素（GCs）导致的早期骨质流失与破骨细胞寿命的延长有关。但是，GCs引起的骨丢失与破骨细胞自噬之间的联系仍有待阐明。通过自噬体检测试剂盒在地塞米松（Dex）诱导的骨质疏松小鼠模型和原代破骨细胞培养物中检测到自噬，并通过Western印迹和免疫染色法检测自噬相关蛋白。通过微CT和TRAP染色检查骨形态。小梁骨微结构恶化，P <0.01）。同时，通过自噬体数量的增加和自噬相关蛋白水平的上调证明了在Dex管理下小鼠中破骨细胞的自噬增加了。此外，在Bexlin 1和LC3-II / LC3-I以及包括Atg1，Atg13和Atg7在内的自噬复合体形成成员的水平增加表明，在原代培养的破骨细胞中证实了Dex处理下自噬的增强。然而，Dex诱导的自噬会抑制原代培养的破骨细胞中PI3K，p-Akt和p-mTOR的表达。使用选择性PTEN抑制剂SF1670激活PI3K / Akt / mTOR途径可逆转Dex治疗下的破骨细胞自噬。我们的研究表明破骨细胞自噬在糖皮质激素诱导的骨丢失中得到增强，