Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells

被引：34

作者：

Manokawinchoke, Jeeranan ^{[1
,2
]}

Nattasit, Praphawi ^{[1
]}

Thongngam, Tanutchaporn ^{[1
]}

Pavasant, Prasit ^{[1
,2
]}

Tompkins, Kevin A. ^{[4
]}

Egusa, Hiroshi ^{[5
]}

Osathanon, Thanaphum ^{[1
,2
,3
]}

机构：

[1] Chulalongkorn Univ, Fac Dent, Excellence Ctr Regenerat Dent, Bangkok 10330, Thailand

[2] Chulalongkorn Univ, Fac Dent, Dept Anat, Bangkok, Thailand

[3] Chulalongkorn Univ, Fac Dent, Craniofacial Genet & Stem Cells Res Grp, Bangkok 10330, Thailand

[4] Chulalongkorn Univ, Off Res Affairs, Fac Dent, Bangkok 10330, Thailand

[5] Tohoku Univ, Grad Sch Dent, Div Mol & Regenerat Prosthodont, Sendai, Miyagi 9808575, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

NOTCH SIGNALING PATHWAY; FIBROBLAST-GROWTH-FACTOR; STEM-CELLS; OSTEOGENIC DIFFERENTIATION; PROMOTES DIFFERENTIATION; DOWN-REGULATION; BONE-FORMATION; INHIBITION; PROLIFERATION; EXPRESSION;

D O I：

10.1038/s41598-017-10638-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a gamma-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.

引用

页数：19

共 66 条

[1] Magnitude-dependent and inversely-related osteogenic/chondrogenic differentiation of human mesenchymal stem cells under dynamic compressive strain [J].