BMP-2 induced Dspp transcription is mediated by Dlx3/Osx signaling pathway in odontoblasts.
BMP-2 induced Dspp transcription is mediated by Dlx3/Osx signaling pathway in odontoblasts.
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成牙本质细胞中 BMP-2 诱导的 Dspp 转录由 Dlx3/Osx 信号通路介导
DOI：
10.1038/s41598-017-10908-8
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发表时间：
2017-09-07
影响因子：
4.6
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Yang G;Yuan G;MacDougall M;Zhi C;Chen S
牙本质唾液酸磷蛋白 (Dspp) 作为成牙本质细胞的分化标志物，受 BMP-2 的调节。然而，其内在机制仍不清楚。转录因子 Dlx3 和 Osx 对于成牙本质细胞分化至关重要。我们假设 BMP-2 对 Dspp 转录的调节是由成牙本质细胞中的 Dlx3 和/或 Osx 介导的。在本研究中，我们发现 BMP-2 在体外和体内刺激成牙本质细胞中 Dlx3 和 Osx 的表达和核转位。 Osx 是 Dlx3 的下游靶标，两者均刺激 Dsp 表达。通过转染含有不同长度的小鼠Dspp启动子的荧光素酶报告，Dlx3和Osx都能够激活从核苷酸(nt)-318到+54的Dspp启动子。通过体内染色质免疫沉淀验证了 Dlx3 和 Osx 与 Dspp 启动子的 nt -318 至 +54 的结合。 EMSA在Dspp启动子上发现了2个Dlx3结合位点和1个Osx结合位点。此外，这些结合位点的确切生物学功能通过定点诱变得到了证实。最后，通过免疫共沉淀检测了成牙本质细胞中Dlx3和Osx之间的蛋白-蛋白相互作用。总之，在本研究中，我们发现了一条新的信号通路，其中 BMP-2 通过 Dlx3/Osx 通路激活 Dspp 基因转录。
Dentin sialophosphoprotein (Dspp) as a differentiation marker of odontoblasts is regulated by BMP-2. However, the intimate mechanism is still unknown. Transcription factors Dlx3 and Osx are essential for odontoblasts differentiation. We hypothesized that BMP-2 regulation of Dspp transcription was mediated by Dlx3 and/or Osx in odontoblasts. In the present investigation, we found that BMP-2 stimulated expression and nuclear translocation of Dlx3 and Osx in odontoblasts both in vitro and in vivo. Osx was a downstream target of Dlx3 and both of them stimulated Dsp expression. Both Dlx3 and Osx were able to activate Dspp promoter from nucleotides (nt) −318 to +54 by transfections of luciferase reports containing different lengths of mouse Dspp promoters. The binding of Dlx3 and Osx with nt −318 to +54 of Dspp promoter was verified by chromatin immunoprecipitation in vivo. Two Dlx3 binding sites and one Osx binding site on Dspp promoter were found by EMSA. Furthermore, the exact biological function of these binding sites was confirmed by site-directed mutagenesis. At last, the protein-protein interaction between Dlx3 and Osx in odontoblasts was detected by co-immunoprecipitation. In conclusion, in this study we found a novel signaling pathway in which BMP-2 activates Dspp gene transcription via Dlx3/Osx pathway.
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DOI：
10.1016/j.biocel.2010.03.020
发表时间：
2010-07
影响因子：
4
作者：
Hosogane, Naobumi;Huang, Zhiping;Rawlins, Bernard A.;Liu, Xia;Boachie-Adjei, Oheneba;Boskey, Adele L.;Zhu, Wei
通讯作者：
Zhu, Wei
影响因子：
1.9
作者：
Butler, WT
通讯作者：
Butler, WT
影响因子：
4.8
作者：
Hassan, Mohammad Q.;Tare, Rahul S.;Lian, Jane B.
通讯作者：
Lian, Jane B.
影响因子：
4.1
作者：
Biver, Emmanuel;Thouverey, Cyril;Caverzasio, Joseph
通讯作者：
Caverzasio, Joseph
影响因子：
0.7
作者：
Liu, F;Woitge, HW;Kream, BE
通讯作者：
Kream, BE