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Yes-associated protein-mediated melatonin regulates the function of periodontal ligament stem cells under oxidative stress conditions

sarah Jonas

BACKGROUND

Human periodontal ligament stem cells (PDLSCs) regenerate oral tissue. In vitro expansion causes replicative senescence in stem cells. This causes intracellular reactive oxygen species (ROS) accumulation, which can impair stem cell function. Tissue engineering efficiency is reduced by exogenous ROS stimulation, which causes premature senescence under oxidative stress. Melatonin (MT), a powerful free radical scavenger, can delay PDLSCs senescence but may not maintain stemness under oxidative stress. This experiment examined the effects of hydrogen peroxide-induced oxidative stress on PDLSCs’ apoptosis, senescence, and stemness.

AIM

To determine if MT can reverse the above effects along with the underlying molecular mechanisms involved.

METHODS

PDLSCs were isolated from human premolars and cultured in different conditions. Flow cytometry was used to characterize the cell surface markers of PDLSCs. Hydrogen peroxide was used to induce oxidative stress in PDLSCs. Cell cycle, proliferation, apoptosis, differentiation, ROS, and senescence-associated β-galactosidase activity were assessed by various assays. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of genes and proteins related to stemness and senescence.

RESULTS

MT increases Yes-associated protein expression and maintains cell stemness in an induced inflammatory microenvironment, which may explain its therapeutic effects. We examined how MT affects PDLSCs aging and stemness and its biological mechanisms.

CONCLUSION

Our study reveals MT’s role in regulating oxidative stress in PDLSCs and Yes-associated protein-mediated activity, providing insights into cellular functions and new therapeutic targets for tissue regeneration.

Key Words: Human periodontal ligament stem cells; Melatonin; Reactive oxygen species; Senescence; Yes-associated protein

Core Tip: While the use of mesenchymal stem cells in preclinical and clinical studies for the treatment of various diseases has provided promising results, the microenvironment of oxidative stress inhibits the efficacy of mesenchymal stem cells-mediated tissue regeneration, which remains a major challenge limiting clinical applications. Our findings provide new insights into melatonin (MT) regulation in the biological functions of oxidative stress-induced periodontal ligament stem cells and elucidate the potential mechanism of Yes-associated protein-mediated MT action. These findings strengthen our comprehension of the role of MT during cellular oxidative stress and provide potential targets for the development of new therapeutic strategies to promote tissue regeneration.