Janjić Klara, Samiei Mohammad, Moritz Andreas, Agis Hermann
Department of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Front Bioeng Biotechnol. 2019 Dec 17;7:430. doi: 10.3389/fbioe.2019.00430. eCollection 2019.
Sclerostin (Sost) and dickkopf (Dkk)-1 are inhibitors of the Wnt signaling pathway that plays a role in regenerative processes. Hypoxia-based strategies are used for regenerative approaches, but the influence of hypoxia on Sost and Dkk-1 production in a pro-inflammatory environment is unclear. The aim of this study was to assess if pro-inflammatory molecules have an influence on Sost and Dkk-1 production in dental pulp cells (DPC) under normoxia and hypoxia. Human DPC were treated with interleukin (IL)-1β, tumor necrosis factor (TNF)α or transforming growth factor (TGF)β, with L-mimosine (L-MIM) or hypoxia or a combination. Sost and Dkk-1 mRNA and protein levels were measured with qPCR and western blot, respectively. TNFα, TGFβ, L-MIM, or combined treatment did not modulate Sost and Dkk-1. IL-1β downregulated Sost at the mRNA level. Hypoxia alone and together with inflammatory markers downregulated Dkk-1 at the mRNA level. Sost and Dkk-1 protein production was below the detection limit. In conclusion, there is a differential effect of hypoxia and IL-1β on the mRNA production of Sost and Dkk-1. Pro-inflammatory molecules do not further modulate the effects of L-MIM or hypoxia on Sost and Dkk-1 production in DPC.
硬化蛋白（Sost）和Dickkopf（Dkk）-1是Wnt信号通路的抑制剂，该信号通路在再生过程中发挥作用。基于缺氧的策略被用于再生方法，但在促炎环境中缺氧对Sost和Dkk-1产生的影响尚不清楚。本研究的目的是评估促炎分子在常氧和缺氧条件下是否对牙髓细胞（DPC）中Sost和Dkk-1的产生有影响。用人白细胞介素（IL）-1β、肿瘤坏死因子（TNF）α或转化生长因子（TGF）β、L-含羞草碱（L-MIM）或缺氧或联合处理人DPC。分别用qPCR和蛋白质印迹法检测Sost和Dkk-1的mRNA和蛋白质水平。TNFα、TGFβ、L-MIM或联合处理均未调节Sost和Dkk-1。IL-1β在mRNA水平下调Sost。单独缺氧以及与炎症标志物共同作用在mRNA水平下调Dkk-1。Sost和Dkk-1的蛋白质产生低于检测限。总之，缺氧和IL-1β对Sost和Dkk-1的mRNA产生有不同的影响。促炎分子不会进一步调节L-MIM或缺氧对DPC中Sost和Dkk-1产生的影响。
