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Metformin Promotes Osteogenic Differentiation by Inducing Autophagy via AMPK/mTOR/p70S6K Signaling Pathway in
Tingting Ye1, Liujin Lu2, Liuqing Guo1
1Department of Geriatric Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Background:
Metformin has unique application potential in bone metabolism, but the effects of metformin on osteoblasts and its mechanism have not been elucidated.
Objective:
The objective of this study was to explore the effects of metformin on osteoblasts and the mechanism underlying these effects.
Methods:
Osteoblasts were treated with metformin, and their effects on osteogenic differentiation and autophagy were monitored. 3-methyladenine (3-MA) was used to investigate the relationship between autophagy and metformin-mediated osteogenic differentiation. Additionally, adenosine 5'-monophosphate-activated protein kinase (AMPK) expression was altered to evaluate the involvement of AMPK/ mammalian target of rapamycin (mTOR)/ phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling in the effects of metformin.
Results:
Our results revealed that metformin promoted osteogenic differentiation, enhanced autophagy, and activated the AMPK pathway. Treatment with 3-MA inhibited the effects of metformin on osteogenic differentiation, autophagy, and AMPK/mTOR/p70S6K signaling in osteoblasts. The effects of AMPK overexpression were similar to those of metformin on osteoblast autophagy and osteogenic differentiation, whereas AMPK deficiency reversed these effects.
Discussion:
Our results reveal the positive effects of metformin on bone metabolism and the underlying mechanisms, which require further validation through in vivo experiments and clinical trials.
Conclusion:
Our findings revealed that AMPK/mTOR/p70S6K signaling is involved in metformin- regulated osteogenic differentiation through the induction of autophagy.
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