title: 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/Ca(2+) 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.
authors.affiliation: Department of Stomatology, Chinese People's Liberation Army 309 Hospital, Beijing 100091, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Stomatology, Chinese People's Liberation Army 309 Hospital, Beijing 100091, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Stomatology, Chinese People's Liberation Army 309 Hospital, Beijing 100091, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Stomatology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Liu
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin