Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla

被引：34

作者：

Jiang, Qingsong ^{[1
,2
]}

Du, Juan ^{[1
]}

Yin, Xiaonan ^{[3
]}

Shan, Zhaochen ^{[4
]}

Ma, Yushi ^{[1
]}

Ma, Ping ^{[1
]}

Du, Juan ^{[1
]}

Fan, Zhipeng ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Mol Lab Gene Therapy & Tooth Regenerat, Lab Mol Signaling & Stem Cells Therapy,Sch Stomat, Tiantan Xili 4, Beijing 100050, Peoples R China

[2] Capital Med Univ, Sch Stomatol, Dept Prosthodont, Beijing 100050, Peoples R China

[3] Qingdao Municipal Med Grp, Dept Stomatol, Qingdao 266071, Shandong, Peoples R China

[4] Capital Med Univ, Sch Stomatol, Dept Oral & Maxillofacial Surg, Beijing 100050, Peoples R China

来源：

MOLECULAR AND CELLULAR BIOCHEMISTRY | 2013年 / 383卷 / 1-2期

关键词：

Smoothened (SMO); Shh signaling; BMP signaling; Mesenchymal stem cells; Osteo/dentinogenic differentiation; SONIC HEDGEHOG; OSTEOGENIC DIFFERENTIATION; STROMAL CELLS; PROLIFERATION; BONE; PURMORPHAMINE; ACTIVATION; EXPRESSION; PERIODONTITIS; REGENERATION;

D O I：

10.1007/s11010-013-1757-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 of GLI1 and SMO were 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.

引用

页码：85 / 93

页数：9

共 44 条

[1]

Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues [J].