Nitrate-Sialin Promotes Dentin Regeneration via Mitochondrial Rewiring

Area of Science:

• Biomedical Science
• Regenerative Medicine
• Dental Research

Background:

• Dental pulp stem cells (DPSCs) lose regenerative capacity with senescence, impairing pulp-dentin homeostasis.
• Current strategies to restore odontogenesis (dentin formation) are limited.

Purpose of the Study:

• To investigate nitrate's role in promoting dentin regeneration.
• To elucidate the Sialin-dependent metabolic mechanisms underlying nitrate's effects on DPSCs.

Main Methods:

• Utilized three senescence models (natural aging, H2O2, etoposide) and Sialin gene silencing.
• Performed untargeted metabolomics and assessed mitochondrial function (ATP, NADH/NAD+, ROS, respiration).
• Employed pharmacologic interventions and a mouse pulp exposure model with Sialin conditional knockout.

Main Results:

• Nitrate reduced senescence and restored odontogenic capacity in DPSCs, dependent on Sialin.
• Nitrate enhanced TCA and pyruvate metabolism, boosting ATP, NADH/NAD+ ratio, and mitochondrial respiration while lowering ROS.
• Local nitrate application accelerated dentin bridge formation in mice, an effect abolished by Sialin deficiency.

Conclusions:

• A nitrate-Sialin-mitochondria axis rejuvenates DPSCs and drives dentin regeneration.
• This pathway restores pulp-dentin homeostasis and presents a potential therapeutic approach for vital pulp therapy.