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Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway
Biology Direct ( IF 5.5 ) Pub Date : 2020-10-07 , DOI: 10.1186/s13062-020-00270-7
Jing Liu 1 , Wuliji Saiyin 1 , Xiaohua Xie 2 , Limin Mao 1 , Lili Li 1, 3
Affiliation  

Amelogenesis imperfecta (AI) is a type of hereditary diseases that manifest defects in the formation or mineralization of enamel. Recently, it is reported that inactivation of FAM20C, a well-known Golgi casein kinase, caused AI. However, the mechanism of it is still unknown. The aim of this study was to explore the molecular mechanism of AI, which caused by ablation of FAM20C. In the Sox2-Cre;Fam20Cfl/fl (cKO) mouse, we found abnormal differentiation of ameloblasts, improper formation and mineralization of enamel, and downregulation of both mRNA and protein level of enamel matrix proteins, including amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM). The levels of BMP2, BMP4 and BMP7, the ligands of BMP signaling pathway, and phosphorylation of Smad1/5/8, the key regulators of BMP signaling pathway, were all decreased in the enamel matrix and the ameloblast of the cKO mice, respectively. The expression of cyclin-dependent kinase inhibitor (P21), muscle segment homeobox genes 2 (Msx2), which are the target genes of the BMP signaling pathway, and laminin 3, the downstream factor of Msx2, were all significantly decreased in the ameloblasts of the cKO mice compared to the control mice. the results of our study suggest that ablation of FAM20C leads to AI through inhibiting the Smad dependent BMP signaling pathway in the process of amelogenesis.

中文翻译:

Fam20c 的消融通过抑制 Smad 依赖性 BMP 信号通路导致牙釉质发育不全

釉质发育不全(AI)是一种遗传性疾病,表现为牙釉质的形成或矿化缺陷。最近,据报道,众所周知的高尔基体酪蛋白激酶 FAM20C 的失活会导致 AI。然而,它的机制仍然未知。本研究的目的是探索由 FAM20C 消融引起的 AI 的分子机制。在 Sox2-Cre;Fam20Cfl/fl (cKO) 小鼠中,我们发现成釉细胞的异常分化、釉质的不当形成和矿化,以及釉质基质蛋白的 mRNA 和蛋白质水平下调,包括釉原蛋白 (AMEL)、成釉细胞 (AMBN) ) 和搪瓷 (ENAM)。BMP2、BMP4和BMP7的水平,BMP信号通路的配体,以及BMP信号通路的关键调节因子Smad1/5/8的磷酸化,分别在 cKO 小鼠的釉质基质和成釉细胞中均减少。细胞周期蛋白依赖性激酶抑制剂 (P21)、BMP 信号通路靶基因肌肉节段同源盒基因 2 (Msx2) 和 Msx2 下游因子层粘连蛋白 3 在成釉细胞中的表达均显着降低。 cKO 小鼠与对照小鼠相比。我们的研究结果表明,消融 FAM20C 通过抑制牙釉质生成过程中的 Smad 依赖性 BMP 信号通路导致 AI。与对照小鼠相比,cKO小鼠的成釉细胞均显着减少。我们的研究结果表明,消融 FAM20C 通过抑制牙釉质生成过程中的 Smad 依赖性 BMP 信号通路导致 AI。与对照小鼠相比,cKO小鼠的成釉细胞均显着减少。我们的研究结果表明,消融 FAM20C 通过抑制牙釉质生成过程中的 Smad 依赖性 BMP 信号通路导致 AI。
更新日期:2020-10-07
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