Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/β-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

Periodontitis-associated alveolar bone loss reflects not only persistent inflammation but also profound metabolic remodeling within the periodontal microenvironment. This review synthesizes current evidence on how lipid metabolic reprogramming regulates periodontal bone remodeling and its therapeutic significance. Under physiological conditions, fatty acid uptake and β-oxidation, lipid droplet turnover, and lipid-derived signaling support osteoblast bioenergetics, stem-cell osteogenesis, and balanced bone remodeling. In contrast, dyslipidemia and chronic inflammatory stress promote the accumulation of free fatty acids, oxidized lipoproteins, cholesterol derivatives, and sphingolipid metabolites, thereby enhancing reactive oxygen species production, lipid peroxidation, inflammasome activation, and pro-inflammatory immune polarization. These changes suppress osteogenic differentiation, stimulate osteoclastogenesis, and impair periodontal regeneration. We further integrate major regulatory networks, including PPARγ–Wnt/β-catenin, AMPK–mTOR, NF-κB/NLRP3, and GSK3β–NRF2/ferroptosis signaling. Therapeutic strategies targeting these lipid–redox–immune circuits include specialized pro-resolving lipid mediators, n-3 polyunsaturated fatty acids, statins, metabolic modulators, and local biomaterial- or nanocarrier-based delivery systems. Accordingly, lipid metabolic reprogramming may provide a framework for developing metabolism-oriented adjunctive and regenerative strategies for periodontitis.