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Published on: May 4, 2018
Treg cell-derived exosomal miR-21 promotes osteogenic differentiation of periodontal ligament stem cells
Yu Xia1, Hao Jiang1, Chen Wang1
1Department of Stomatology, Eighth Medical Center of Chinese PLA General Hospital, No. 17, Heishanhu Road, Haidian District, Beijing, 100091, China.
Background:
Regulatory T (Treg) cells are essential for maintaining immune tolerance and have been implicated in tissue regeneration; however, their role in periodontal regeneration remains poorly understood. This study aimed to elucidate the effect of Treg cell-derived exosomes (Treg-Exos), particularly those carrying microRNA-21 (miR-21), on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and periodontal tissue regeneration.
Methods:
After co-culturing Treg cells or Treg-Exos with PDLSCs respectively in vitro, the osteogenic differentiation of treated PDLSCs was assessed through Alkaline phosphatase (ALP) activity, Alizarin Red staining, and the expression of osteogenic markers runt-related transcription factor 2 (Runx-2) and Osterix. The functional role of miR-21 in Treg-Exos was assessed via gain- and loss-of-function experiments, involving transfection of Treg cells with miR-21 mimics or inhibitors. In vivo, a mice periodontal defect model was established via silk ligation and Porphyromonas gingivalis inoculation. Subsequently, Treg-Exos were locally administered into defects to assess their potential in promoting periodontal tissue regeneration. The regenerative efficacy was evaluated using micro-CT and histological analysis.
Results:
Treg cell levels were significantly elevated in periodontitis patients compared to healthy controls. Both Treg cells and Treg-Exos markedly promoted the osteogenic differentiation of PDLSCs in vitro, as evidenced by increased ALP activity, enhanced mineralization, and upregulated Runx-2/Osterix expression. Exosomes derived from miR-21-overexpressing Treg cells further promoted PDLSC osteogenesis, whereas exosomes with miR-21 knockdown exhibited an inhibitory effect. In vivo, Treg-Exos injection alleviated periodontal damage and improved tissue morphology compared to PBS controls, as demonstrated by micro-CT and histological analyses.
Conclusion:
Treg cell-derived exosomal miR-21 promotes the osteogenic differentiation of PDLSCs, enhancing periodontal tissue regeneration in vivo, suggesting that Treg cells and their exosomal miR-21 may serve as promising therapeutic targets for periodontitis.
