Abstract
AIM: The regeneration ability of dental pulp stem cells (DPSCs) is essential for vital pulp preservation therapy, but may be disrupted by inflammatory senescence. Mitochondrial dynamics proteins maintain mitochondrial homeostasis and could alleviate inflammatory senescence, though their impact on DPSCs' functions and clinical prognosis remains unclear. MATERIALS AND METHODS: Human inflammatory and normal dental pulp were ethically collected from clinic-extracted wisdom teeth to detect inflammation, senescence, mitochondrial dynamics, and oxidative stress markers. The DPSCs' inflammatory senescence model was induced by Escherichia coli lipopolysaccharide, and mitochondrial fusion and fission proteins were modulated with inhibitors to study their relationship with inflammatory senescence. RESULTS: The pulpitis group exhibited inflammatory cell infiltration and overexpressed inflammatory factors, oxidative stress, and senescence markers compared to normal tissue. The same trends were observed in the cell model. Lipopolysaccharide downregulated cell proliferation and differentiation, and upregulated senescence and apoptosis, with decreased OPA1 and increased DRP1. Further reducing fusion exacerbated these phenomena, while reducting fission relieved them. CONCLUSIONS: This study highlights the critical role of mitochondrial fusion and fission in DPSCs inflammatory senescence. Enhancing mitochondrial fusion (via OPA1) or suppressing fission (via DRP1) may counteract senescence and restore DPSCs regenerative capacity. These findings provide a potential therapeutic strategy to preserve pulp vitality and improve regenerative outcomes. CLINICAL RELEVANCE: Maintaining DPSCs functionality is crucial for successful regenerative endodontic treatments. Since inflammation-induced senescence impairs DPSCs regeneration, targeting mitochondrial dynamics - particularly by promoting fusion or inhibiting fission - could enhance pulp tissue repair and long-term tooth preservation. This evidence suggests mitochondrial modulation could be explored for pulpitis management and dental pulp vitality preservation.