TNF-α 通过 NF-κB 信号通路触发人牙髓干细胞的成骨分化。

TNF-α triggers osteogenic differentiation of human dental pulp stem cells via the NF-κB signalling pathway.

机构信息

Department of Stomatology, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Cell Biol Int. 2013 Dec;37(12):1267-75. doi: 10.1002/cbin.10141. Epub 2013 Oct 21.

Abstract

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs) characterised by self-renewal and multi-lineage differentiation, including chondrocytes, adipocytes, neural cells and osteoblasts, which make it an attractive choice for tissue engineering purposes. Tumour necrosis factor α (TNF-α) had the positive effect on the mineralisation of bone marrow MSCs and stromal cells derived from human adipose tissue. However, the effect of TNF-α on DPSCs is unclear. We found that TNF-α activated the NF-κB pathway during the osteogenic differentiation of DPSCs. TNF-α also increased mineralisation and the expression of bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and collagen type I (COL I) during this process. PDTC, an NF-κB inhibitor, blocked the osteogenic differentiation induced by TNF-α. No effect of TNF-α on proliferation of DPSCs or cell cycle was detected. In summary, TNF-α promotes mineralisation and mineralisation-related gene expression through the NF-κB signalling pathway in DPSCs, which may provide a foundation for autologous transplantation of DPSCs.

摘要

牙髓干细胞（DPSCs）是一种间充质干细胞（MSCs），具有自我更新和多向分化的特性，包括软骨细胞、脂肪细胞、神经细胞和成骨细胞，这使其成为组织工程的理想选择。肿瘤坏死因子 α（TNF-α）对骨髓间充质干细胞和来源于人脂肪组织的基质细胞的矿化有积极作用。然而，TNF-α 对 DPSCs 的影响尚不清楚。我们发现 TNF-α 在 DPSCs 的成骨分化过程中激活了 NF-κB 通路。TNF-α 还增加了矿化以及骨形态发生蛋白 2（BMP2）、碱性磷酸酶（ALP）、 runt 相关转录因子 2（RUNX2）和胶原 I（COL I）的表达。NF-κB 抑制剂 PDTC 阻断了 TNF-α 诱导的成骨分化。TNF-α 对 DPSCs 的增殖或细胞周期没有影响。总之，TNF-α 通过 NF-κB 信号通路促进 DPSCs 的矿化和矿化相关基因表达，这可能为 DPSCs 的自体移植提供基础。