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

Journal of Molecular Histology - Tập 46 - Trang 409-420 - 2015
Zhenjie Qin1, Zhixiu Fang1, Lei Zhao1, Jing Chen1, Yuanteng Li2, Guangyun Liu3
1Department of Stomatology, Zoucheng People’s Hospital, Zoucheng, People’s Republic of China
2Department of Pharmacy, Zoucheng People’s Hospital, Zoucheng, People’s Republic of China
3Department of Obstetrics and Gynecology, Zoucheng People’s Hospital, Zoucheng, People’s Republic of China

Tóm tắt

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.

Tài liệu tham khảo

Gronthos S, Mankani M, Brahim J, Robey PG, Shi S (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 97:13625–13630

Li B, Shi M, Li J, Zhang H, Chen B, Chen L, Gao W, Giuliani N, Zhao RC (2007) Elevated tumor necrosis factor-alpha suppresses TAZ expression and impairs osteogenic potential of Flk-1 + mesenchymal stem cells in patients with multiple myeloma. Stem Cells Dev 16:921–930