Metformin promotes osteogenic differentiation and protects against oxidative stress-induced damage in periodontal ligament stem cells via activation of the Akt/Nrf2 signaling pathway
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Abstract
Periodontal ligament stem cell (PDLSC)-based tissue engineering is an important method
for regenerating lost bone in periodontitis. Maintaining or enhancing the osteogenic
differentiation of PDLSCs, as well as enhancing the resistance of PDLSCs to oxidative
stress, is necessary in this process. As a common hypoglycemic drug, metformin has
been reported to have multiple effects on cell functions. This study found that low
concentrations of metformin did not affect cell proliferation but did inhibit adipogenic
differentiation and promote osteogenic differentiation of PDLSCs. This positive effect
was associated with activation of Akt signaling by metformin. Moreover, applying metformin
as either a pretreatment or co-treatment could reduce the amount of reactive oxygen
species, enhance antioxidant capacity, and rescue the cell viability and osteogenic
differentiation that were negatively affected by H2O2-induced oxidative stress in
PDLSCs. In addition, metformin was found to activate the Nrf2 signaling pathway in
PDLSCs, and knockdown of Nrf2 by siRNA impaired the protective effect of metformin.
Taken together, these results indicate that metformin not only promotes osteogenic
differentiation of PDLSCs, but also protects PDLSCs against oxidative stress-induced
damage, suggesting that metformin could be potentially useful in promoting PDLSC-based
bone regeneration in the treatment of periodontitis.