ET-1 Promotes Differentiation of Periodontal Ligament Stem Cells into Osteoblasts through ETR, MAPK, and Wnt/β-Catenin Signaling Pathways under Inflammatory Microenvironment

Abstract

Periodontitis is a kind of chronic inflammatory disease that affects the tooth-supporting tissues. ET-1 is related to periodontitis and involved in the regulation of cytokines, but the mechanisms remain unclear. The aim of this study is to investigate how ET-1 affects proinflammatory cytokine expression and differentiation in human periodontal ligament stem cells (PDLSCs). PDLSCs were isolated from the periodontal ligament tissues of periodontitis patients and then treated with ET-1 (1, 10, or 100 nM) for 12 h, 24 h, or 72 h. The osteogenic potential of PDLSCs was tested using ALP staining. TNF-α, IL-1β, and IL-6 levels were evaluated by ELISA and western blot. Runx2, OCN, and COL1 mRNA and western levels were detected by RT-PCR and western blot, respectively. To examine the signaling pathways and molecular mechanisms involved in ET-1-mediated cytokine expression and osteogenic differentiation, ETR pathway, MAPKs pathway, Wnt/β-catenin pathway, and Wnt/Ca2+ pathway were detected by RT-PCR and western blot, respectively. ET-1 promoted differentiation of PDLSCs into osteoblasts by increasing secretion of TNF-α, IL-1β, and IL-6 in a dose- and time-dependent manner. ET-1 also increased expression of Runx2, OCN, and COL1. ET-1 promotes differentiation of PDLSCs into osteoblasts through ETR, MAPK, and Wnt/β-catenin signaling pathways under inflammatory microenvironment.

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway

“…AuNPs activate the p38 pathway and increase the level of RUNX2. In order to identify the signaling pathway involved in mediating the effect of AuNPs upon osteogenic differentiation in hPDLSCs, western blotting was used to examine the levels of p38, ERK1/2, and JNK1/2 at 24 h and COL1, OSX and RUNX2 at 7 days, all of which have been previously demonstrated to be closely associated with osteogenesis (22)(23)(24). As presented in Fig.…”

Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration

“…H2S increased hydroxyl radical production in isolated mouse heart mitochondria and F2-isoprostanes in brains and hearts of mice [98]. H2S plays an important role in the proliferation and differentiation of human periodontal ligament stem cells (PDLSCs) [99, 100]. Human PDLSCs express both CBS and CSE and produce H2S.…”

Inflammation has synergistic effect with nicotine in periodontitis by up‐regulating the expression of α7 nAChR via phosphorylated GSK‐3β

“…It has been confirmed that there might be a bidirectional regulation between α7 nAChR and certain inflammatory factors like interleukin‐1β (IL‐1β) and tumour necrosis factor‐α (TNF‐α) . Moreover, the inflammatory response of PDLSCs could activate multiple signalling pathways, such as those involving glycogen synthase kinase‐3β (GSK‐3β) . Furthermore, in the central nervous system, increased expression of phosphorylated GSK‐3β can up‐regulate the expression and promote the function of α7 nAChR, thus suppressing the progression of degenerative diseases .…”

“…16,17 Moreover, the inflammatory response of PDLSCs could activate multiple signalling pathways, such as those involving glycogen synthase kinase-3β (GSK-3β). 18 Furthermore, in the central nervous system, increased expression of phosphorylated GSK-3β can up-regulate the expression and promote the function of α7 nAChR, thus suppressing the progression of degenerative diseases. 19 Our previous study indicated that TNF-α significantly increases phosphorylated GSK-3β levels in bone marrow-derived mesenchymal stem cells and PDLSCs.…”