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2018 ; 22
(7
): 3442-3451
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Stathmin inhibits proliferation and differentiation of dental pulp stem cells via
sonic hedgehog/Gli
#MMPMID29655218
Ma D
; Yu H
; Xu S
; Wang H
; Zhang X
; Ning T
; Wu B
J Cell Mol Med
2018[Jul]; 22
(7
): 3442-3451
PMID29655218
show ga
The mineralization of dental pulp stem cells is an important factor in the tissue
engineering of teeth, but the mechanism is not yet obvious. This study aimed to
identify the effect of Stathmin on the proliferation and osteogenic/odontoblastic
differentiation of human dental pulp stem cells (hDPSCs) and to explore whether
the Shh signalling pathway was involved in this regulation. First, Stathmin was
expressed in the cytoplasm and on the cell membranes of hDPSCs by cell
immunofluorescence. Then, by constructing a lentiviral vector, the expression of
Stathmin in hDPSCs was inhibited. Treatment with Stathmin shRNA (shRNA-Stathmin
group) inhibited the ability of hDPSCs to proliferate, as demonstrated by a CCK8
assay and flow cytometry analysis, and suppressed the osteogenic/odontoblastic
differentiation ability, as demonstrated by alizarin red S staining and
osteogenic/odontoblastic differentiation-related gene (ALP, BSP, OCN, DSPP)
activity, compared to that of hDPSCs from the control shRNA group. Molecular
analyses showed that the Shh/GLI1 signalling pathway was inhibited when Stathmin
was silenced, and purmorphamine, the Shh signalling pathway activator, was added
to hDPSCs in the shRNA-Stathmin group, real-time PCR and Western blotting
confirmed that expression of Shh and its downstream signalling molecules PTCH1,
SMO and GLI1 increased significantly. After activating the Shh signalling
pathway, the proliferation of hDPSCs increased markedly, as demonstrated by a
CCK8 assay and flow cytometry analysis; osteogenic/odontoblastic
differentiation-related gene (ALP, BSP, OCN, DSPP) expression also increased
significantly. Collectively, these findings firstly revealed that
Stathmin-Shh/GLI1 signalling pathway plays a positive role in hDPSC proliferation
and osteogenic/odontoblastic differentiation.