Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla
Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla
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Shh 信号受到 BMP 信号的负调控，抑制根尖乳头间充质干细胞的骨/牙本质分化潜能
DOI：
10.1007/s11010-013-1757-9
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发表时间：
2013-11-01
影响因子：
4.3
通讯作者：
Fan, Zhipeng
中科院分区：
文献类型：
--
作者：
Jiang, Qingsong;Du, Juan;Fan, Zhipeng
来源于牙齿组织的间充质干细胞（MSCs）显示出用于牙齿相关组织再生的前景，但其定向分化的分子机制仍不清楚，限制了其用途。Sonic Hedgehog（Shh）信号通路是调控细胞分化和成骨的主要信号通路。我们发现，当Shh信号被人重组SHH-N蛋白或通过在来自顶乳头的干细胞（SCAPs）中过表达活性突变体M2-Smoothened（SMO）激活时，关键下游转录因子和Shh信号的标记物GLI 1被上调。随后，体外骨/牙本质分化和体内成骨在SCAPs中被抑制。BMP信号下调GLI 1和SMO的表达，上调SCAPs的成骨/牙本质分化。这些结果提供了深入了解Shh信号在源自牙齿组织的MSC的定向分化中的作用，并建议可能的靶基因用于优化牙齿来源的干细胞用于组织再生应用。
Mesenchymal stem cells (MSCs) derived from dental tissues show promise for use in tooth-related tissue regeneration, but the molecular mechanisms underlying their directed differentiation remain unclear, limiting their usefulness. Sonic Hedgehog (Shh) signaling is a major signaling pathway that regulates cell differentiation and osteogenesis. We found that when Shh signaling was activated by human recombinant SHH-N protein or by overexpression of active mutant M2-Smoothened (SMO) in stem cells from apical papilla (SCAPs),GLI1,a key downstream transcription factor and a marker of Shh signaling, was upregulated. Subsequently, in vitro osteo/dentinogenic differentiation and in vivo osteogenesis were inhibited in SCAPs. Moreover, the expression ofGLI1andSMOwere downregulated by BMP signaling while osteo/dentinogenic differentiation in SCAPs was upregulated. These results provide insights into the role of Shh signaling in the directed differentiation of MSCs derived from dental tissues and suggest possible target genes for optimizing the use of stem cells of dental origin for tissue regeneration applications.