title: High dose of TNF-α suppressed osteogenic differentiation of human dental pulp stem cells by activating the Wnt/β-catenin signaling.
abstract: Dental pulp stem cells (DPSCs) were a clonogenic, highly proliferative cells capable of self-renewal and multi-lineage differentiation including chondrocytes, adipocytes, neural cells and osteoblasts, which make it an attractive choice for bone regeneration and repair of craniofacial defects. Recent studies showed that tumor necrosis factor α (TNF-α) may affect osteoclastogenesis and bone formation. However, the effect and mechanism of TNF-α on DPSCs is not clear. In this study, we found that low dose TNF-α promoted mineralization and high dose TNF-α suppressed osteogenic differentiation of DPSCs. Levels of ALP, Osteopontin, Osteocalcin, Osterix and Runx2 were up-regulated in DPSCs treated with TNF-α at low concentration, while down-regulated in DPSCs treated with TNF-α at high concentration. Blockade of Wnt/β-catenin signaling reversed the inhibitory effect observed on osteogenic differentiation of DPSCs treated with TNF-α at high concentration. In addition, we did not detect any proliferative effect of TNF-α on DPSCs by cell cycle and cell counts analysis. In summary, our data suggested that high concentration TNF-α suppressed mineralization and mineralization-related gene expressions through the Wnt/β-catenin signaling in DPSCs. Our findings may provide a foundation for autologous transplantation of DPSCs.
authors.affiliation: Department of Stomatology, Zoucheng People's Hospital, Zoucheng, 273500, Shandong, People's Republic of China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Qin
authors.forename: Zhixiu
authors.initials: Z
authors.lastname: Fang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yuanteng
authors.initials: Y
authors.lastname: Li
authors.forename: Guangyun
authors.initials: G
authors.lastname: Liu
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin