High dose of TNF-α suppressed osteogenic differentiation of human dental pulp stem cells by activating the Wnt/β-catenin signaling

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 alpha (TNF-alpha) may affect osteoclastogenesis and bone formation. However, the effect and mechanism of TNF-alpha on DPSCs is not clear. In this study, we found that low dose TNF-alpha promoted mineralization and high dose TNF-alpha suppressed osteogenic differentiation of DPSCs. Levels of ALP, Osteopontin, Osteocalcin, Osterix and Runx2 were up-regulated in DPSCs treated with TNF-alpha at low concentration, while down-regulated in DPSCs treated with TNF-alpha at high concentration. Blockade of Wnt/beta-catenin signaling reversed the inhibitory effect observed on osteogenic differentiation of DPSCs treated with TNF-alpha at high concentration. In addition, we did not detect any proliferative effect of TNF-alpha on DPSCs by cell cycle and cell counts analysis. In summary, our data suggested that high concentration TNF-alpha suppressed mineralization and mineralization-related gene expressions through the Wnt/beta-catenin signaling in DPSCs. Our findings may provide a foundation for autologous transplantation of DPSCs.