Proanthocyanidin enhances the endogenous regeneration of alveolar bone by elevating the autophagy of PDLSCs

Abstract

ObjectiveThis study aimed to investigate the effect of proanthocyanidin (PA) on osteogenesis mediated by periodontal ligament stem cells (PDLSCs) and endogenous alveolar bone regeneration.BackgroundLeveraging the osteogenic potential of resident stem cells is a promising strategy for alveolar bone regeneration. PA has been reported to be effective in osteogenesis. However, the effect and mechanism of PA on the osteogenic differentiation of PDLSCs remain elusive.MethodsHuman PDLSCs were treated with various doses of PA to assess the cell proliferation using Cell Counting Kit‐8. The osteogenic differentiation ability was detected by qRT‐PCR analysis, western blot analysis, Alizarin red S staining, and Alkaline Phosphatase staining. The level of autophagy was evaluated by confocal laser scanning microscopy, transmission electron microscopy, and western blot analysis. RNA sequencing was utilized to screen the potential signaling pathway. The alveolar bone defect model of rats was created to observe endogenous bone regeneration.ResultsPA activated intracellular autophagy in PDLSCs, resulting in enhanced osteogenic differentiation. Moreover, this effect could be abolished by the autophagy inhibitor 3‐Methyladenine. Mechanistically, the PI3K/Akt/mTOR pathway was negatively correlated with PA‐mediated autophagy activation. Lastly, PA promoted the alveolar bone regeneration in vivo, and this effect was reversed when the autophagy process was blocked.ConclusionPA may activate autophagy by inhibiting PI3K/Akt/mTOR signaling pathway to promote the osteogenesis of PDLSCs and enhance endogenous alveolar bone regeneration.

From Basic Science to Clinical Practice: A Review of Current Periodontal/Mucogingival Regenerative Biomaterials

“…[ 282 ] In recent years, researchers found that medications, and especially host modulators, show great potential in resolving or inhibiting the periodontal inflammatory process, particularly in the early phases of periodontitis combined with non‐surgical periodontal treatment. [ 283 , 284 , 285 , 286 , 287 , 288 , 289 ] These host modulators include statins like atorvastatin, rosuvastatin, and simvastatin, as well as alendronate and metformin. [ 80 , 89 , 92 , 95 , 96 , 98 , 99 , 105 , 290 , 291 , 292 , 293 , 294 , 295 , 296 ] Statins exhibit anti‐inflammatory and immunomodulatory properties while inhibiting osteoclasts and stimulating bone morphogenetic proteins.…”

Insights and Advancements in Periodontal Tissue Engineering and Bone Regeneration

“…The association of FGF-2 with heparin significantly decreases the degradation of FGF-2 and greatly enhances its mitogenic activity. Additionally, heparin sulfate proteoglycans act as cofactors in the interactions between FGF2 and FGF receptors, facilitating the activation of downstream signaling pathways [55][56][57]. In general, clinical data substantiates the safety and effectiveness of employing FGF-2 in the treatment of intraosseous defects in periodontal conditions.…”

“…This product incorporates β-tricalcium phosphate as a scaffold [50,51,55]. Residing within the ζ-granules of platelets and discharged upon activation, PDGF has been demonstrated to stimulate DNA synthesis, chemotaxis, and the synthesis of collagen and glycosaminoglycans in fibroblasts [56][57][58]. Laboratory analyses conducted in vitro have shown that PDGF significantly enhances the expression of stem cell markers and promotes the proliferation of mesenchymal stem cells (MSCs) isolated from PDL tissues [59].…”

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation

“…Proanthocyanidins can promote osteogenic differentiation of human periodontal ligament cells in inflammatory environments by inhibiting the NF-κB signaling pathway [ 24 ]. Moreover, our recent study found that proanthocyanidins activate the autophagy of PDLSCs by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby promoting osteogenesis and enhancing endogenous alveolar bone regeneration [ 25 ]. However, the specific mechanism by which proanthocyanidins promote the osteogenic differentiation of PDLSCs in the inflammatory state remains to be refined.…”