Phosphatase and tensin homolog (PTEN) is a critical regulator of cell proliferation, differentiation, and inflammatory balance. However, its downstream proteomic effects in periodontal ligament stem cells (PDLSCs) remain poorly understood. This study aimed to elucidate the proteomic alterations induced by PTEN inhibition and identify potential molecular pathways underlying periodontal regeneration. PDLSCs were treated with 5 μM VO-OHpic for 24 hours, followed by proteomic profiling using mass spectrometric analysis. The resulting proteomic data were analysed using Heatmapper, Metascape, and WebGestalt (WEB-based Gene Set Analysis Toolkit) databases, as well as Cytoscape, to evaluate protein expression patterns and protein-protein interaction networks. Proteomic analysis identified 7,525 proteins across all samples, with 3,497 proteins commonly expressed between groups. In the VO-OHpic-treated cells, proteins related to cytoskeletal dynamics (ACTR2, FNDC3A), vesicular transport (GGA1, RAB9A), and signal transduction (TRAF3IP3, GJB3) were upregulated. Enrichment analysis identified potential biological pathways related to membrane trafficking, secretion, and regulation of MAPK and Wnt signalling. Conversely, proteins linked to transcriptional and metabolic regulation (GLIS3, PHGDH, NADSYN1) and membrane trafficking (SNX1, REEP1) were downregulated. Cytokine signalling and interferon pathways were explored as the potential pathways involved in these downregulated proteins. In conclusion, PTEN inhibition by VO-OHpic was associated with proteomic changes in PDLSCs linked to regenerative phenotype, including the modulation of MAPK and Wnt signalling pathways alongside alterations in immune and metabolic pathways. These findings suggest that PTEN may function as a modulator balancing inflammatory regulation and differentiation processes, providing mechanistic insight into its potential role in periodontal tissue regeneration.

Japan's marked decline in early childhood caries (ECC) has been documented through uniquely comprehensive national dental examinations, with standardized population surveys conducted continuously for more than four decades. This perspective discusses how Japan achieved sustained reduction in ECC despite the absence of community water fluoridation and historically limited use of toothpaste with effective fluoride concentration in infancy. Drawing on national surveillance and epidemiological evidence, I consider how changes in dietary patterns, caregiver practices, oral health behaviours, and broader social conditions may have contributed to a less cariogenic environment for young children. Importantly, this experience does not diminish the established effectiveness of fluoride-based interventions; rather, it highlights complementary, system-level factors operating over long time horizons. Japan's experience may inform context-sensitive ECC prevention strategies, particularly in settings where fluoride use is limited, unevenly implemented, or difficult to sustain.