MicroRNA hsa-let-7b suppresses the odonto/osteogenic differentiation capacity of stem cells from apical papilla by targeting MMP1.

MicroRNA let-7 family acts as the key regulator of the differentiation of mesenchymal stem cells (MSCs). However, the influence of let-7b on biological characteristics of stem cells from apical papilla (SCAPs) is still controversial. In this study, the expression of hsa-let-7b was obviously downregulated during the osteogenic differentiation of SCAPs. SCAPs were then infected with hsa-let-7b or hsa-let-7b inhibitor lentiviruses. The proliferation ability was determined by CCK-8 and flow cytometry. The odonto/osteogenic differentiation capacity was analyzed by alkaline phosphatase (ALP) activity, alizarin red staining, Western blot assay, and real-time RT-PCR. Bioinformatics analysis was used to screen out the target of hsa-let-7b and the target relationship was confirmed by dual luciferase reporter assay. Hsa-let-7b was of no influence on the proliferation of SCAPs. Interferential expression of hsa-let-7b increased the ALP activity as well as the formation of calcified nodules of SCAPs. Moreover, the mRNA levels of osteoblastic markers (ALP, RUNX2, OSX, OPN, and OCN) were upregulated while the protein levels of DSPP, ALP, RUNX2, OSX, OPN, and OCN also increased considerably. Conversely, overexpression of hsa-let-7b inhibited the odonto/osteogenic differentiation capacity of SCAPs. Bioinformatics analysis revealed a putative binding site of hsa-let-7b in the matrix metalloproteinase 1 (MMP1) 3'-untranslated region (3'-UTR). Dual luciferase reporter assay confirmed that hsa-let-7b targets MMP1. The odonto/osteogenic differentiation ability of SCAPs ascended after repression of hsa-let-7b, which was then reversed after co-transfection with siMMP1. Together, hsa-let-7b can suppress the odonto/osteogenic differentiation capacity of SCAPs by targeting MMP1.

Wang Y ，Pang X ，Wu J ，Jin L ，Yu Y ，Gobin R ，Yu J ... -  《-》

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla.

Ma S ，Liu G ，Jin L ，Pang X ，Wang Y ，Wang Z ，Yu Y ，Yu J ... -  《Scientific Reports》

Yunnan Baiyao Conditioned Medium Promotes the Odonto/Osteogenic Capacity of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway.

Pang X ，Wang Y ，Wu J ，Zhou Z ，Xu T ，Jin L ，Yu Y ，Li Z ，Gobin R ，Xue C ，Yu J ... -  《-》

Effects of canonical NF-κB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla.

Li J ，Yan M ，Wang Z ，Jing S ，Li Y ，Liu G ，Yu J ，Fan Z ... -  《-》

Oestrogen receptor α regulates the odonto/osteogenic differentiation of stem cells from apical papilla via ERK and JNK MAPK pathways.

Oestrogen receptor (ER) is a common nucleus receptor that is essential for the regulation of cell growth, proliferation and differentiation. This study was to examine whether ERα can affect the proliferation and odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs). Stem cells from apical papillas were isolated, purified and then transfected with ERα lentiviruses. The proliferation capacity was investigated by cell counting kit-8 (CCK-8) assay and flow cytometry. The odonto/osteogenic differentiation ability was analysed by alkaline phosphatase (ALP) activity, alizarin red staining, western blot assay (WB) and real-time RT-PCR. MAPK pathway and its downstream transcriptional factors were explored by WB assay. As indicated by CCK-8 assay and flow cytometry, ERα had no significant effect on the proliferation of SCAPs. When ERα was overexpressed, the ALP activity and the formation of calcified nodules were significantly enhanced in SCAPs. Moreover, the odonto/osteogenic markers (DMP1/DMP1, DSPP/DSP, RUNX2/RUNX2, OCN/OCN) in SCAPs were significantly up-regulated at both mRNA and protein levels. On the contrary, the odonto/osteogenic differentiation ability of SCAPs was remarkably inhibited after suppression of ERα. Mechanistically, the protein levels of phosphorylated ERK and JNK significantly increased after ERα overexpression. Moreover, some downstream transcriptional factors of MAPK pathway were simultaneously activated by ERα overexpression. Together, the data accumulated here indicated that ERα can enhance the odonto/osteogenic differentiation of SCAPs via ERK and JNK MAPK pathways.

Wang Y ，Lu Y ，Li Z ，Zhou Y ，Gu Y ，Pang X ，Wu J ，Gobin R ，Yu J ... -  《-》