The Self-Assembling Peptide P11-4 Induces the Expression of Mineralization-Related Genes in Odontoblasts Independently of Metabolic Alterations

(1) Background: The synthetic eleven-amino acid peptide P11-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P11-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P11-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P11-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca2+ influx and a slight increase in ROS. Among the 84 genes examined, P11-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P11-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P11-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells.