Human gingival mesenchymal stem cell‐derived exosomes cross‐regulate the Wnt/β‐catenin and NF‐κB signalling pathways in the periodontal inflammation microenvironment

Abstract Aim To examine the immunomodulatory effect of exosomes originating from gingival mesenchymal stem cells (GMSC‐Exo) on periodontal bone regeneration and its role in the regulation of the nuclear‐factor kappaB (NF‐κB) and Wnt/β‐catenin pathways in the periodontal inflammatory microenvironment. Materials and Methods First, periodontal ligament stem cells (PDLSCs) were treated with GMSC‐Exo or Porphyromonas gingivalis ‐derived lipopolysaccharide ( P.g ‐LPS) in vitro. Quantitative real‐time PCR (qRT‐PCR) and western blot were carried out to detect the expressions of osteogenic differentiation‐related factors in cells. Further, PDLSCs were treated with P.g ‐LPS or inhibitors. The expression of NF‐κB pathway‐related factors as well as of Wnt/β‐catenin pathway‐related factors were detected by qRT‐PCR and western blot. Results GMSC‐Exo treatment promoted the expression of osteogenic differentiation‐related factors within PDLSCs in both normal and inflammatory environments. Further investigations showed that GMSC‐Exo could also inhibit the P.g‐ LPS‐induced activation of the NF‐κB pathway, leading to the up‐regulation of the Wnt/β‐catenin pathway. When the Wnt/β‐catenin signalling was blocked, the inhibitory effect of GMSC‐Exo on the NF‐κB pathway was abolished. Conclusions GMSC‐Exo could promote the osteogenic differentiation of PDLSCs. There could be mutually exclusive regulatory roles between the NF‐κB and Wnt/β‐catenin signalling pathways in a periodontal inflammatory environment. GMSC‐Exo exhibited an effective cross‐regulation ability for both pathways.