Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways.
Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways.
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1 - 磷酸鞘氨醇通过与AKT信号通路相关联，阻碍牙髓干细胞的成骨分化。
DOI：
10.1038/s41368-022-00173-5
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发表时间：
2022-04-22
影响因子：
14.9
通讯作者：
Chang, Eun-Ju
中科院分区：
文献类型：
--
作者：
Choi, Bongkun;Kim, Ji-Eun;Park, Si-On;Kim, Eun-Young;Oh, Soyoon;Choi, Hyuksu;Yoon, Dohee;Min, Hyo-Jin;Kim, Hyung-Ryong;Chang, Eun-Ju
鞘氨醇-1-磷酸（S1 P）是一种重要的脂质介质，调节与组织工程和再生医学相关的多种细胞内信号传导途径。然而，S1 P在牙髓干细胞（DPSC）及其成骨分化中的确切功能尚不清楚。本研究旨在探讨S1 P/S1 P受体（S1 PR）介导的细胞信号转导在DPSCs成骨分化中的作用，阐明其基本信号转导途径。我们的研究结果表明，S1 P处理的DPSCs表现出低分化率的成骨表型与成骨相关的基因表达和AKT活化显着减少。值得注意的是，S1 PR 1/S1 PR 3和S1 PR 2激动剂均显著下调成骨基因的表达并抑制AKT活化，导致DPSC的成骨能力减弱。最重要的是，AKT激活剂完全消除了S1 P介导的成骨细胞标志物的下调，并部分阻止了成骨过程中S1 P介导的衰减效应。有趣的是，促炎性TNF-α细胞因子促进巨噬细胞向DPSC的浸润，并诱导DPSC和巨噬细胞中S1 P的产生。我们的研究结果表明，炎症条件下S1 P的升高抑制了负责再生牙髓的DPSC的成骨能力。
Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
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影响因子：
7.5
作者：
Gibon E;Lu L;Goodman SB
通讯作者：
Goodman SB
影响因子：
4.1
作者：
Aronin, Caren E. Petrie;Sefcik, Lauren S.;Botchwey, Edward A.
通讯作者：
Botchwey, Edward A.
影响因子：
12.7
作者：
Fernandes, Gabriela;Yang, Shuying
通讯作者：
Yang, Shuying
影响因子：
--
作者：
Chen XY;Xu SZ;Wang XW;Yang XY;Ma L;Zhang L;Yang GJ;Yang F;Wang LH;Zhang XL;Ting K;Gao CY;Mou XZ;Gou ZR;Zou H
通讯作者：
Zou H
DOI：
10.1084/jem.20101474
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ishii M;Kikuta J;Shimazu Y;Meier-Schellersheim M;Germain RN
通讯作者：
Germain RN