Epigenetic regulation can dynamically adjust the gene expression program of cell fate decision according to the cellular microenvironment. Emerging studies have shown that metabolic activities provide fundamental components for epigenetic modifications and these metabolic-sensitive epigenetic events dramatically impact the cellular function of stem cells. Dental mesenchymal stem cells are promising adult stem cell resource for in situ injury repair and tissue engineering. In this review, we discuss the impact of metabolic fluctuations on epigenetic modifications in the oral and maxillofacial regions. The principles of the metabolic link to epigenetic modifications and the interaction between metabolite substrates and canonical epigenetic events in dental mesenchymal stem cells are summarized. The coordination between metabolic pathways and epigenetic events plays an important role in cellular progresses including differentiation, inflammatory responses, and aging. The metabolic-epigenetic network is critical for expanding our current understanding of tissue homeostasis and cell fate decision and for guiding potential therapeutic approaches in dental regeneration and infectious diseases.
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