1,25-Dihydroxyvitamin D3 Alleviates High Glucose-Induced Oxidative Stress and Rescues Osteogenic Differentiation of Human Periodontal Ligament Stem Cells via the NRF2/HO-1 Signaling Pathway

Abstract Periodontitis is a chronic infectious disease caused by dental plaque biofilms, driving progressive destruction of periodontal supporting tissues. Diabetes mellitus is recognized as a major risk factor for this disease. Hyperglycemia-induced oxidative stress severely impairs the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), thereby hindering periodontal bone regeneration. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been confirmed to possess both antioxidant and pro-osteogenic activities; however, its specific regulatory effects on hPDLSCs under high-glucose conditions remain poorly elucidated. This study aimed to construct a high glucose-induced oxidative stress injury model in hPDLSCs to investigate the effects of 1,25(OH)2D3 on oxidative stress and osteogenic differentiation, and to elucidate the underlying molecular mechanisms, so as to provide a theoretical basis and identify novel therapeutic targets for periodontal bone regeneration in diabetes-associated periodontitis. Our results demonstrated that high glucose exposure inhibited the proliferation, migration and osteogenesis of hPDLSCs, while concurrently increasing oxidative stress and inflammatory responses. 1,25(OH)2D3 alleviates high glucose-induced oxidative stress damage and rescues the impaired osteogenic differentiation of hPDLSCs via activating the NRF2/HO-1 signaling pathway. Collectively, these findings indicate that 1,25(OH)2D3 represents a promising therapeutic candidate for periodontal bone regeneration in patients with diabetic periodontitis.