间充质
细胞生物学
生物
Wnt信号通路
牙乳头
诺金
成牙本质细胞
牙髓干细胞
干细胞
同源盒
Notch信号通路
牙本质涎磷蛋白
内斯汀
牙本质形成
骨形态发生蛋白
间充质干细胞
牙髓(牙)
病理
神经干细胞
信号转导
遗传学
基因表达
医学
基因
作者
Chen Zhou,Guodong Yang,Mo Chen,Zhong Chen,Ling He,Lin Xiang,Danying Chen,Jiayu Ling,Jeremy J. Mao
出处
期刊:Biomaterials
[Elsevier]
日期:2015-09-01
卷期号:63: 35-46
被引量:41
标识
DOI:10.1016/j.biomaterials.2015.06.004
摘要
LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo. Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activated Wnt and TGFβ pathways, and its attenuation upregulated multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling.
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