High glucose downregulates the effects of autophagy on osteoclastogenesis via the AMPK/mTOR/ULK1 pathway
- Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning (China)
- Department of Orthopedics, The Fourth Hospital of China Medical University, 4 Chongshandong Road, Shenyang, Liaoning, 110032 (China)
Highlights: • High glucose downregulates AMPK/mTOR/ULK pathway in osteoclasts. • Inhibition of AMPK/mTOR/ULK pathway suppresses autophagy in glucose-mediated osteoclastogenesis. • Autophagy has a positive correlation with glucose-mediated osteoclastogenesis. 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.
- OSTI ID:
- 23105617
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 2; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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