自噬
破骨细胞
PI3K/AKT/mTOR通路
化学
细胞生物学
巴非霉素
骨吸收
信号转导
内分泌学
内科学
组织蛋白酶K
蛋白激酶A
组织蛋白酶
细胞生长
细胞
溶酶体
吸收
蛋白激酶B
骨重建
程序性细胞死亡
兰克尔
糖尿病
酸性磷酸酶
小干扰RNA
激酶
细胞周期
死孢子体1
生物化学
细胞凋亡
作者
Zhenyu Cai,Bo Yang,Yingxu Shi,Weilin Zhang,Fei Liu,Wei Zhao,Maowei Yang
标识
DOI:10.1016/j.bbrc.2018.04.052
摘要
Diabetes is a chronic disease that disrupts the balance between bone formation and bone desorption, which can lead to osteoporosis, increasing the risk of fracture. However, compared with osteoblasts, the biological effects of hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5, 20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell proliferation was measured with the cell counting kit-8 assay, and osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining and bone resorption assays, as well as protein cathepsin K expression. Compound C, the AMP-activated protein kinase (AMPK) pathway inhibitor, was used to examine the relationship between the AMPK/mTOR/ULK1 signaling pathway and autophagy in osteoclasts. Autophagy was evaluated with transmission electron microscopy and immunofluorescence microscopy and associated proteins were detected with western blotting. The pharmacological autophagic reagents bafilomycin A1, 3-methyladenine, and rapamycin were used to determine the effect of autophagy on osteoclastogenesis. Our results showed that glucose negatively affected osteoclast formation and function but did not affect the proliferation of RAW264.7 cells. Suppression of the AMPK/mTOR/ULK1 signaling axis decreased autophagy in glucose-mediated osteoclast. Furthermore, High levels of glucose decreased autophagy level in osteoclasts. Additionally, interfering with autophagy affected osteoclast formation and function. These findings clarify the mechanisms underlying the effects of glucose-mediated osteoclastogenesis and will help identify novel therapeutic strategies for the protection of skeletal health in diabetic osteoporosis.
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