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 pathwayrelated 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 differentiationrelated 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/βcatenin signalling pathways in a periodontal inflammatory environment. GMSC-Exo exhibited an effective cross-regulation ability for both pathways.

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

“…Studies have shown that Pg‐LPS‐induced inflammation can inhibit osteogenic differentiation of periodontal ligament stem cells, and our results further confirm this conclusion 36,37 . hPDLSCs were isolated according to previous studies and passaged after the cells had crawled out and reached 90% confluence.…”

“…Studies have shown that Pg-LPS-induced inflammation can inhibit osteogenic differentiation of periodontal ligament stem cells, and our results further confirm this conclusion. 36,37 hPDLSCs were isolated according to previous studies and passaged after the cells had crawled out and reached 90% confluence. When hPDLSCs were stimulated with 10 μg/mL Pg-LPS for 7 days, qRT-PCR demonstrated that Pg-LPS stimulation increased the mRNA expression of IL-6 and IL-8, which are inflammatory markers (Figure 4A).…”

NF-κB p65 and TCF-4 interactions are associated with LPS-stimulated IL-6 secretion of macrophages

“…Crosstalk between NF-κB and Wnt/β-catenin pathways in inflammation has been suggested previously by various groups [ 17 , 18 ]. However, both positive and negative correlations have been observed depending on the cell or tissue types or inflammation status [ 27 ].…”

“…Regarding the cross-regulation of the NF-κB and Wnt/β-catenin pathways, a number of articles suggest both positive and negative correlations [ [16] , [17] , [18] , [19] , [20] ]. In LPS-treated BEAS-2B human bronchial epithelial cells, the siRNA knockdown of β-catenin attenuated not only the Wnt/β-catenin pathway, but also the NF-κB pathway [ 20 ].…”

Emerging roles of exosomes in oral diseases progression

“… 172 Controlling the anomaly inflammatory changes in periodontal cells and the microenvironment is the premise of periodontitis regenerative treatment. 11 Exhibiting periodontal anti-inflammatory effect, gingival mesenchymal stem cell (GMSC)-secreted exosomes target NF-κB signaling and Wnt5a in a periodontal microenvironment 173 , 174 and modulate macrophage polarization in high-lipid-level 175 or TNF-α pre-condition circumstances. 176 A similar macrophage transformation also occurs with chitosan hydrogel-engineered DPSC-derived exosomes via miR-1246.…”