Abstract
Periodontitis is a chronic infectious disease involving periodontal tissues. Periodontal ligament cells (PDLCs) play an important role in the regeneration of periodontal tissue. However, senescent PDLCs have an impeded regenerative potential. Metformin has been reported to prevent senescence at both the cellular and individual levels. The objectives of the present study were to evaluate the effects of metformin on cellular senescence in human PDLCs (hPDLCs) under oxidative stress. hPDLCs were pretreated with metformin, followed by H2O2 exposure. The cell viability, oxidative damage, cellular senescence and osteogenic potential were detected. To inhibit autophagy, hPDLCs were treated with 3-methyladenine before metformin treatment. The present study revealed that H2O2 exposure inhibits proliferation, increased lysosomal β-galactosidase activity, augments reactive oxidative species (ROS) accumulation, elevates the oxidative damage, stimulates the expression of senescence-related genes and impedes the activity of the osteogenic differentiation of hPDLCs. Metformin pretreatment could partly reverse the detrimental influences of H2O2 on hPDLCs. Moreover, metformin could stimulate autophagy, whereas the inhibition of autophagy with 3-methyladenine reversed the anti-senescence effects of metformin on hPDLCs under oxidative stress. The present study manifested that metformin could alleviate oxidative stress-induced senescence via stimulating autophagy and could partially recover the osteogenic potential of hPDLCs, possibly providing a reference for the discovery of periodontal treatment from the perspective of antisenescence.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant Nos. 81771082 and 81570981), Chongqing Research Program of Basic Research and Frontier Technology (Grant No. cstc2017jcyjBX0019), and the Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016 (Grant No. CXTDG201602006).
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Kuang, Y., Hu, B., Feng, G. et al. Metformin prevents against oxidative stress-induced senescence in human periodontal ligament cells. Biogerontology 21, 13–27 (2020). https://doi.org/10.1007/s10522-019-09838-x
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DOI: https://doi.org/10.1007/s10522-019-09838-x