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

TNF-α triggers osteogenic differentiation of human dental pulp stem cells via the NF-κB signalling pathway
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DOI:
10.1002/cbin.10141
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发表时间:
2013-12-01
影响因子:
3.9
通讯作者:
Gu, Zhifeng
Gu, Zhifeng
中科院分区:
生物学4区
文献类型:
--
作者:
Feng, Xingmei;Feng, Guijuan;Gu, Zhifeng

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牙髓干细胞(Dental pulp stem cells,DPSCs)是一类具有自我更新和多向分化潜能的间充质干细胞(mesenchymal stem cells,MSCs),可分化为软骨细胞、脂肪细胞、神经细胞和成骨细胞等,是组织工程领域的理想选择。肿瘤坏死因子(TNF-α)对骨髓间充质干细胞和人脂肪组织来源的基质细胞的矿化有积极作用。然而,TNF-α对DPSC的影响尚不清楚。我们发现在DPSCs的成骨分化过程中,TNF-α激活了NF-B通路。在此过程中,TNF-α还增加了矿化和骨形态发生蛋白2(BMP 2)、碱性磷酸酶(ALP)、侏儒相关转录因子2(RUNX 2)和I型胶原(COL I)的表达。NF-B抑制剂PDTC可阻断TNF-α诱导的成骨分化。TNF-α对DPSCs的增殖及细胞周期无明显影响。总之,TNF-α通过NF-β信号通路促进DPSC的矿化和矿化相关基因的表达,这可能为DPSC的自体移植提供基础。
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 (TNF-) had the positive effect on the mineralisation of bone marrow MSCs and stromal cells derived from human adipose tissue. However, the effect of TNF- on DPSCs is unclear. We found that TNF- activated the NF-B pathway during the osteogenic differentiation of DPSCs. TNF- 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-B inhibitor, blocked the osteogenic differentiation induced by TNF-. No effect of TNF- on proliferation of DPSCs or cell cycle was detected. In summary, TNF- promotes mineralisation and mineralisation-related gene expression through the NF-B signalling pathway in DPSCs, which may provide a foundation for autologous transplantation of DPSCs.