Human periodontal ligament stem cells and metformin to enhance periodontal regeneration in rats
Abstract
BACKGROUND: Effective periodontal repair and regeneration remain a critical clinical need, requiring strategies that address the complex regeneration of both bone and cementum within the periodontal complex. The objectives of this study were to: (1) develop a novel strategy for periodontal regeneration via human periodontal ligament stem cells (hPDLSCs) and metformin; (2) investigate the metformin regulatory mechanism via the ERK1/2 signaling pathway that promotes periodontal regeneration; (3) evaluate the effectiveness of the combination of hPDLSCs and metformin in promoting the repair of periodontal defects in rats.
METHODS: hPDLSCs were cultured in medium with graded metformin doses (0-600 μM) to determine the optimal concentration via CCK-8 assay, scratch assay and osteogenic/cementogenic differentiation analyses. ERK1/2 phosphorylation, induced by the optimal metformin concentration, and its inhibition by U0126 (10 μM) were analyzed via Western blot to assess its role in promoting osteogenesis and cementogenesis. In vivo, 30 rats with periodontal defects were divided into five groups: (1) Blank control; (2) Matrigel only; (3) Matrigel + metformin; (4) Matrigel + hPDLSCs; (5) Matrigel + Metformin + hPDLSCs. Micro-CT and histological staining were performed at 6 weeks to evaluate periodontal regeneration. Data were analyzed using one-way and two-way ANOVA (p < 0.05).
RESULTS: 100 μM metformin optimally promoted hPDLSCs proliferation, migration, osteogenesis, and…
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