Epigenetic Approaches for Regeneration of the Dentin-Pulp Complex
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The dentin-pulp complex (DPC) is essential for tooth vitality and reparative responses after injury; however, its inherent regenerative capacity is limited. Advances in epigenetics offer promising strategies to enhance DPC regeneration by modulating gene expression without altering DNA sequences. This review synthesizes current knowledge of principal epigenetic mechanisms—DNA methylation, histone modifications, and non-coding RNAs—that regulate dental pulp stem cell fate, emphasizing their interactions with signaling pathways such as Wnt, BMP/TGF-β, and Notch. Regulatory factors, including DNA methyltransferases (DNMTs), histone deacetylases (HDACs), and microRNAs, modulate stem cell plasticity through transcription factors such as RUNX2, thereby promoting odontogenic differentiation. The therapeutic potential and limitations of pharmacological epigenetic modulators, such as HDAC and DNMT inhibitors, are examined alongside advanced approaches including CRISPR/dCas9-mediated epigenome editing and multi-omics profiling for patient-specific regenerative interventions. Preclinical studies indicate that these strategies enhance mineral deposition, vascularization, and pulp-like tissue regeneration. In conclusion, epigenetic modulation provides a reversible and biologically relevant means to promote functional repair of the DPC, with significant implications for future regenerative dental therapies.
Abstract
The dentin-pulp complex (DPC) is essential for tooth vitality and reparative responses after injury; however, its inherent regenerative capacity is limited. Advances in epigenetics offer promising strategies to enhance DPC regeneration by modulating gene expression without altering DNA sequences. This review synthesizes current knowledge of principal epigenetic mechanisms—DNA methylation, histone modifications, and non-coding RNAs—that regulate dental pulp stem cell fate, emphasizing their interactions with signaling pathways such as Wnt, BMP/TGF-β, and Notch. Regulatory factors, including DNA methyltransferases (DNMTs), histone deacetylases (HDACs), and microRNAs, modulate stem cell plasticity through transcription factors such as RUNX2, thereby promoting odontogenic differentiation. The therapeutic potential and limitations of pharmacological epigenetic modulators, such as HDAC and DNMT inhibitors, are examined alongside advanced approaches including CRISPR/dCas9-mediated epigenome editing and multi-omics profiling for patient-specific regenerative interventions. Preclinical studies indicate that these strategies enhance mineral deposition, vascularization, and pulp-like tissue regeneration. In conclusion, epigenetic modulation provides a reversible and biologically relevant means to promote functional repair of the DPC, with significant implications for future regenerative dental therapies.