scholarly journals GSK3β Rephosphorylation Rescues ALPL Deficiency Induced-impairment of Odontoblastic Differentiation of DPSCs

2020 ◽  
Author(s):  
Liqiang Zhang ◽  
Jiangdong Zhao ◽  
Jiayi Dong ◽  
Yuting Liu ◽  
Kun Xuan ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Alveolar Bone ◽  
Immunofluorescent Staining ◽  
Deciduous Teeth ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Alizarin Red ◽  
Odontoblastic Differentiation ◽  
Pulp Cells ◽  
Licl Treatment

Abstract Background: Premature exfoliation of deciduous teeth is a common manifestation in childhood patients with Hypophosphatasia (HPP), which is an autosomal inherited disease caused by ALPL mutations. Dysplasia of cementum, dentin and alveolar bone have been proposed to be the main reasons for the exfoliation of teeth, while the extraordinarily complex intracellular mechanisms remain elusive. Dental pulp stem cells (DPSCs) have been demonstrated to successfully regenerate functional pulp-dentin like tissue. Dental pulp cells derived from HPP patients impaired mineralization, however insight into the deeper mechanism is still unclear. Methods: The effects of ALPL on odontoblastic differentiation of DPSCs from HPP patient were assessed by Alizarin Red staining, immunofluorescent staining, Western blot and RT-PCR, and micro-CT assays. Results: Here, we found DPSCs from HPP patient exhibited low ALP activity and impaired odontoblastic differentiation. Meanwhile, we found that loss of function of ALPL reduced phosphorylation of GSK3β in DPSCs. While GSK3β rephosphorylation improved odontoblastic differentiation of HPP DPSCs with LiCl treatment. Finally, we demonstrated systemic LiCl injection ameliorated tooth associated defects in ALPL+/- mice by enhanced phosphorylation of GSK3β in teeth. Conclusions: Our study indicates that ALPL regulates odontoblastic differentiation of DPSCs, and provides useful information for understanding how ALPL deficiency leaded to tooth dysplasia and, ultimately, may inform efforts at improvement tooth defects in HPP patients.

scholarly journals GSK3β rephosphorylation rescues ALPL deficiency-induced impairment of odontoblastic differentiation of DPSCs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Liqiang Zhang ◽  
Jiangdong Zhao ◽  
Jiayi Dong ◽  
Yuting Liu ◽  
Kun Xuan ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Alveolar Bone ◽  
Immunofluorescent Staining ◽  
Deciduous Teeth ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Alizarin Red ◽  
Odontoblastic Differentiation ◽  
Pulp Cells ◽  
Licl Treatment

Abstract Background Premature exfoliation of the deciduous teeth is a common manifestation in childhood patients with hypophosphatasia (HPP), which is an autosomal inherited disease caused by ALPL mutations. Dysplasia of the cementum, dentin, and alveolar bone has been proposed to be the main reasons for the exfoliation of teeth, while the extraordinarily complex intracellular mechanisms remain elusive. Dental pulp stem cells (DPSCs) have been demonstrated to successfully regenerate functional pulp-dentin-like tissue. Dental pulp cells derived from HPP patients impaired mineralization; however, insight into the deeper mechanism is still unclear. Methods The effects of ALPL on odontoblastic differentiation of DPSCs from HPP patient were assessed by Alizarin Red staining, immunofluorescent staining, Western blot and RT-PCR, and micro-CT assays. Result Here, we found DPSCs from HPP patient exhibited low ALP activity and impaired odontoblastic differentiation. Meanwhile, we found that loss of function of ALPL reduced phosphorylation of GSK3β in DPSCs. While GSK3β rephosphorylation improved odontoblastic differentiation of HPP DPSCs with LiCl treatment. Finally, we demonstrated systemic LiCl injection ameliorated tooth-associated defects in ALPL+/− mice by enhanced phosphorylation of GSK3β in the teeth. Conclusions Our study indicates that ALPL regulates odontoblastic differentiation of DPSCs and provides useful information for understanding how ALPL deficiency led to tooth dysplasia and, ultimately, may inform efforts at improvement tooth defects in HPP patients.

Baicalein Promotes Angiogenesis and Odontoblastic Differentiation via the BMP and Wnt Pathways in Human Dental Pulp Cells

2016 ◽  
Vol 44 (07) ◽  
pp. 1457-1472 ◽  
Author(s):  
Sang-Im Lee ◽  
Sun-Young Kim ◽  
Kyung-Ran Park ◽  
Eun-Cheol Kim
Keyword(s):  
Dental Pulp ◽  
Marker Genes ◽  
Signal Pathways ◽  
Dependent Manner ◽  
Dental Pulp Cells ◽  
Alizarin Red ◽  
Human Dental Pulp Cells ◽  
Odontoblastic Differentiation ◽  
Human Dental Pulp ◽  
Pulp Cells

Baicalein is an active flavonoid extracted from the root of Scutellaria baicalensis that has anticancer and anti-inflammatory properties; its effects on osteoblastic and angiogenic potential are controversial. The aim of this study was to investigate the effects of baicalein on odontoblastic differentiation and angiogenesis and the underlying mechanism in human dental pulp cells (HDPCs). Baicalein (1–10[Formula: see text][Formula: see text]M) had no cytotoxic effects and promoted alkaline phosphatase (ALP) activity, mineralization assayed by Alizarin Red-S staining, and the mRNA expression of marker genes, in a concentration-dependent manner. In addition, baicalein upregulated angiogenic factors and increased in vitro capillary-like tube formation. Moreover, baicalein upregulated bone morphogenetic protein (BMP)-2 mRNA and phosphorylation of Smad 1/5/8 and Wnt ligand mRNA, glycogen synthase kinase-3, and nuclear [Formula: see text]-catenin. The odontogenic and angiogenic effects of baicalein were abolished by the BMP antagonist noggin and the Wnt/[Formula: see text]-catenin receptor antagonist DKK-1. These results demonstrate that baicalein promoted odontoblastic differentiation and angiogenesis of HDPCs by activating the BMP and Wnt/[Formula: see text]-catenin signal pathways. Our findings suggest that baicalein may contribute to dental pulp repair and regenerative endodontics.

scholarly journals Sclerostin promotes human dental pulp cells senescence

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5808 ◽  
Author(s):  
Yanjing Ou ◽  
Yi Zhou ◽  
Shanshan Liang ◽  
Yining Wang
Keyword(s):  
Dental Pulp ◽  
Wnt Signaling Pathway ◽  
Dental Pulp Cells ◽  
Differentiation Potential ◽  
Human Dental Pulp Cells ◽  
Qrt Pcr ◽  
Odontoblastic Differentiation ◽  
Human Dental Pulp ◽  
Pulp Cells

Background Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation. Methods Immunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential. Results By immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway. Discussion The increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.

scholarly journals Dental pulp cells that express adeno-associated virus serotype 2-mediated BMP-7 gene enhanced odontoblastic differentiation

2014 ◽  
Vol 33 (5) ◽  
pp. 656-662
Author(s):  
Wei QIN ◽  
Haiyan ZHU ◽  
Lingling CHEN ◽  
Xiaoting YANG ◽  
Qiting HUANG ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Dental Pulp Cells ◽  
Adeno Associated Virus ◽  
Odontoblastic Differentiation ◽  
Virus Serotype ◽  
Pulp Cells

The role of SDF-1 and CXCR4 on odontoblastic differentiation in human dental pulp cells

2013 ◽  
Vol 47 (6) ◽  
pp. 534-541 ◽  
Author(s):  
D. S. Kim ◽  
Y. S. Kim ◽  
W. J. Bae ◽  
H. J. Lee ◽  
S. W. Chang ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Odontoblastic Differentiation ◽  
Human Dental Pulp ◽  
Pulp Cells

scholarly journals Lipopolysaccharide stimulation improves the odontoblastic differentiation of human dental pulp cells

2014 ◽  
Vol 11 (5) ◽  
pp. 3547-3552 ◽  
Author(s):  
YIHUA HUANG ◽  
HONGWEI JIANG ◽  
QIMEI GONG ◽  
XUYAN LI ◽  
JUNQI LING
Keyword(s):  
Dental Pulp ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Odontoblastic Differentiation ◽  
Human Dental Pulp ◽  
Pulp Cells

17β-Estradiol induces odontoblastic differentiation via activation of the c-Src/MAPK pathway in human dental pulp cells

2015 ◽  
Vol 93 (6) ◽  
pp. 587-595 ◽  
Author(s):  
Su Mi Woo ◽  
Kyung Joo Seong ◽  
Sang Jin Oh ◽  
Hong Ju Park ◽  
Sun Hun Kim ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Dental Pulp Cells ◽  
Human Dental Pulp Cells ◽  
Odontoblastic Differentiation ◽  
Alp Activity ◽  
Human Dental Pulp ◽  
Pulp Cells ◽  
17Β Estradiol

The present study is aimed at investigating the effects of the exogenous estrogen 17β-estradiol (E2) on odontoblastic differentiation in human dental pulp cells (HDPCs) immotalized with hTERT gene and their molecular mechanism. Proliferation was detected by BrdU assay, and odontoblast differentiation induction was evaluated by the expression of dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP) and dentin matrix protein1 (DMP1), and alkaline phosphatase (ALP) activity and mineralization. Estrogen receptor-α (ER-α), c-Src, and mitogen-activated protein kinases (MAPKs) were examined and their inhibitors were used to determine the roles on odontogenic induction. E2 significantly promoted the HDPC proliferation, which was mediated by extracellular signal-related kinase 1/2. E2 upregulated DSPP, DSP, and DMP1 as the odontogenic differentiation markers and enhanced ALP activity and mineralization. E2 increased phosphorylation of ER-α and fulvestrant, an ER downregulator, significantly downregulated DSPP, DMP1, and DSP induced by E2. Moreover, E2 treatment activated c-Src and MAPKs upon odontogenic induction, whereas chemical inhibition of c-Src and MAPKs decreased expression of DSPP, DMP1, and DSP and mineralization augmented by E2. Moreover, fulvestrant reduced E2-induced phosphorylation of c-Src and MAPK and inhibition of c-Src by PP2 attenuated activation of MAPKs during E2-induced odontoblastic differentiation. Taken together, these results indicated that E2 stimulates odontoblastic differentiation of HDPCs via coordinated regulation of ER-α, c-Src, and MAPK signaling pathways, which may play a key role in the regeneration of dentin.

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