Melatonin regulation and the function of the periodontal ligament: Future perspective and challenges

The present article reviews the emerging role of melatonin (MT) and the Hippo- Yes-associated protein signaling pathway in periodontal regeneration, high- lighting their potential to delay the aging process of periodontal ligament stem cells (PDLSCs). Oxidative stress and cellular senescence are major obstacles in regenerative therapies, especially in an aging population. MT, a potent antioxidant, restores the morphology, proliferation, and osteogenic differentiation potential of PDLSCs under oxidative stress conditions. Recent research highlights how MT enhances PDLSC stemness by upregulating Yes-associated protein ex- pression, offering a promising therapeutic strategy to antagonize tissue dege- neration. In addition, the article discusses the growing interest in probiotics as a complementary approach to improve oral microbiota and support tissue regeneration. The integration of MT with traditional and novel therapeutic approaches may pave the way for innovative preventive or active treatments in periodontology, aimed at reducing oxidative stress. Future research needs to focus on translating these findings into clinical applications and promoting a deeper understanding of periodontal regeneration and cellular aging.