The Role of PIN1 on Odontogenic and Adipogenic Differentiation in Human Dental Pulp Stem Cells

Lee, Young-Man; Shin, Seung‐Yun; Jue, Seong-Suk; Kwon, Il Keun; Cho, Eunhee; Cho, Eui-Sic; Park, Sanghyuk; Kim, Eun-Cheol

doi:10.1089/scd.2013.0339

Cited by 41 publications

(44 citation statements)

References 44 publications

(59 reference statements)

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“…The NF-κB pathway has been reported to be extensively involved in differentiation of osteoblasts and odontoblasts [31,32]. For example, Hess et al showed that enhanced NF-κB activity in human mesenchymal stem cells increases osteogenic differentiation [33].…”

Section: Discussionmentioning

confidence: 99%

Human Dental Pulp Stem Cells via the NF-κB Pathway

Gu¹,

Ran²,

Qin³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Odontogenic differentiation of human dental pulp stem cells (HDPSCs) is regulated by multiple factors and signaling molecules. However, their regulatory mechanisms are not completely understood. In this study, we investigated the role of Zinc finger and BTB domain-containing 20 (ZBTB20) in odontoblastic differentiation of HDPSCs. Methods: HDPSCs were obtained from human third molars and ZBTB20 expression was examined by qRT-PCR and western blot. Their osteo/odontogenic differentiation and the involvement of NF-κB pathway were subsequently investigated. Results: The expression of ZBTB20 is upregulated in a time-dependent manner during odontogenic differentiation of hDPSCs. Inhibition of ZBTB20 reduced osteogenic medium (OM)-induced odontogenic differentiation, reflected in decreased alkaline phosphatase (ALP) activity, mineralized nodule formation and mRNA expression of odonto/osteogenic marker genes. In contrast, overexpression of ZBTB20 enhanced ALP activity, mineralization and the expression of differentiation marker genes. Furthermore, the expression of IκBa was increased by ZBTB20 silencing in HDPSCs, whereas ZBTB20 overexpression decreased IκBa and enhanced nuclear NF-κB p65. Inhibition of the NF-κB pathway significantly suppressed the odontogenic differentiation of HDPSCs induced by ZBTB20. Conclusion: This study shows for the first time that ZBTB20 plays an important role during odontoblastic differentiation of HDPSCs and may have clinical implications for regenerative endodontics.

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Section: Discussionmentioning

confidence: 99%

Human Dental Pulp Stem Cells via the NF-κB Pathway

Gu¹,

Ran²,

Qin³

et al. 2015

Cell Physiol Biochem

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“…The cells were cultured in -MEM supplemented with 10% FBS, 100 U/ml penicillin, and 100 g/ml streptomycin in a humidified atmosphere of 5% CO 2 at 37 C. In order to induce differentiation, the cells were cultured in osteogenic medium (OM; 50 g/mL ascorbic acid, 10 mM -glycerophosphate and 100 nM dexamethasone), as previously described. 20 The cells were seeded in the prepared cement samples and were then cultured for 1, 2, 4, and 8 h. For the cell adhesion assay, the cultured cells were treated with 3-(4,5-dimethylthiazol-2-yl) 2,5diphenyltetrazolium bromide (MTT) solution. After 4 h of reaction, the culture medium was removed and the precipitated formazan crystals were dissolved by adding 200 L dimethyl sulfoxide solution, after which the colorimetric activity was recorded using a microplate reader at 570 nm.…”

Section: Methodsmentioning

confidence: 99%

Stimulation of Odontogenesis and Angiogenesis via Bioactive Nanocomposite Calcium Phosphate Cements Through Integrin and VEGF Signaling Pathways

Lee¹,

Lee²,

El‐Fiqi³

et al. 2016

j biomed nanotechnol

Self Cite

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Formulating self-setting calcium phosphate cements (CPCs) with secondary phases particularly in the nanoscale order holds great promise to improve biological properties. Here, we focus on the effect that bioactive glass nanoparticles (BGN) incorporated in CPC compositions can have on the proliferation, odontogenic differentiation, and angiogenic stimulation of stem cells derived from human dental pulp (HDPSCs). These odontogenic and angiogenic events are of special importance in the dentin-pulp regeneration processes. In comparison to pure CPCs, nanocomposite cements exhibit a significantly improved proliferation of HDPSCs, and the improvement is more significant as the BGN content increases. The nanocomposite cements substantially enhance the adhesion of cells, and significantly up-regulate odontogenic differentiation, including alkaline phosphatase (ALP) activity and the expressions of odontogenic genes (sialophosphoprotein, dentin matrix protein I, ALP, osteopontin and osteocalcin). Furthermore, the use of nanocomposite cements result in stimulation of angiogenic gene expression (VEGF, FGF-2, VEGFRs, PECAM-1, and VE-cadherin) and protein production (VEGF, VEGFR-1). The angiogenic stimulation by the HDPSCs significantly affects the endothelial cell behaviors, that is, the endothelial cell migration and the tubular network formation are substantially improved when treated with HDPSC-conditioned medium, particularly with the help of nanocomposite cements. The integrin and VEGF signaling pathways are reasoned for the stimulation of the odontogenesis and angiogenesis of cells, where the nanocomposite cements up-regulate the integrin subsets α1, α2, α3, and β1, and activate the integrin downstream signal pathways, such as p-FAK, p-Akt, p-paxillin, JNK, EK, and NF-κB, as well as other nuclear transcriptional factors, including CREB, STAT-3, and ELK-1. The current results indicate that the new formulation of the nanocomposite self-setting cements might provide some beneficial microenvironments for the regenerative processes of dentin-pulp complex tissues.

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“…PIN1, a peptidyl-prolyl cis/trans isomerase, acts as an important modulator of odontogenic and adipogenic differentiation of hDPSCs. BMP, Wnt/β--catenin, MAPK and NF-κB pathway are involved in PIN1-mediated differentiation of hDPSCs [ 102 ]. Moreover, WNT5α mRNA and protein expressions rapidly increased in response to LPS treatment in a time-and dose-dependent manner.…”

Section: Signaling Pathway Networkmentioning

confidence: 95%