Open AccessIGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla
Author(s) -
Shuai Ma,
Genxia Liu,
Jin Lin,
Xiyao Pang,
Yanqiu Wang,
Zilu Wang,
Yang Yu,
Jinhua Yu
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep36922
Subject(s) - runx2 , mesenchymal stem cell , mapk/erk pathway , western blot , microbiology and biotechnology , stem cell , chemistry , downregulation and upregulation , cellular differentiation , kinase , transcription factor , biology , biochemistry , gene
Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/ RUNX2 , OSX/ OSX , OCN/ OCN , COL-I/ COL-I , DSPP/ DSP , and DMP-1/ DMP-1 ) in IGF-1 treated SCAPs were significantly upregulated in Let-7c -low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c -low SCAPs but inhibited in Let-7c -over SCAPs. Together, the IGF-1/IGF-1R/ hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways.