Effects of p-Cresol on Senescence, Survival, Inflammation, and Odontoblast Differentiation in Canine Dental Pulp Stem Cells

Aging, defined by a decrease in the physical and functional integrity of the tissues, leads to age-associated degenerative diseases. There is a relation between aged dental pulp and the senescence of dental pulp stem cells (DPSCs). Therefore, it is important to investigate the molecular processes underlying the senescence of DPSCs to elucidate the dental pulp aging mechanisms. p-Cresol (PC), a uremic toxin, is strongly related to cellular senescence. Here, age-related phenotypic changes including senescence, apoptosis, inflammation, and declining odontoblast differentiation in PC-treated canine DPSCs were investigated. Under the PC condition, cellular senescence was induced by decreased proliferation capacity and increased cell size, senescence-associated β-galactosidase (SA-β-gal) activity, and senescence markers p21, IL-1β, IL-8, and p53. Exposure to PC could stimulate inflammation by the increased expression of IL-6 and cause the distraction of the cell cycle by the increased level of Bax protein and decreased Bcl-2. The levels of odontoblast differentiation markers, dentin sialophosphoprotein (DSPP), dentin matrix protein 1, and osterix, were decreased. Consistent with those findings, the alizarin red staining, alkaline phosphatase, and DSPP protein level were decreased during the odontoblast differentiation process. Taken together, these findings indicate that PC could induce cellular senescence in DPSCs, which may demonstrate the changes in aging dental pulp.

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Odontoblast-Like Cells Differentiated from Dental Pulp Stem Cells Retain Their Phenotype after Subcultivation

International Journal of Cell Biology ◽

10.1155/2018/6853189 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 12

Author(s):

Paula A. Baldión ◽

Myriam L. Velandia-Romero ◽

Jaime E. Castellanos

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Materials ◽

Dental Pulp Stem Cells ◽

Cell Physiology ◽

Pulp Tissue ◽

Alizarin Red ◽

Dentin Matrix Protein ◽

Mineral Deposition

Odontoblasts, the main cell type in teeth pulp tissue, are not cultivable and they are responsible for the first line of response after dental restauration. Studies on dental materials cytotoxicity and odontoblast cells physiology require large quantity of homogenous cells retaining most of the phenotype characteristics. Odontoblast-like cells (OLC) were differentiated from human dental pulp stem cells using differentiation medium (containing TGF-β1), and OLC expanded after trypsinization (EXP-21) were evaluated and compared. Despite a slower cell growth curve, EXP-21 cells express similarly the odontoblast markers dentinal sialophosphoprotein and dentin matrix protein-1 concomitantly with RUNX2 transcripts and low alkaline phosphatase activity as expected. Both OLC and EXP-21 cells showed similar mineral deposition activity evidenced by alizarin red and von Kossa staining. These results pointed out minor changes in phenotype of subcultured EXP-21 regarding the primarily differentiated OLC, making the subcultivation of these cells a useful strategy to obtain odontoblasts for biocompatibility or cell physiology studies in dentistry.

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Biomimetic Approach to Perforation Repair Using Dental Pulp Stem Cells and Dentin Matrix Protein 1

Journal of Endodontics ◽

10.1016/j.joen.2011.05.019 ◽

2011 ◽

Vol 37 (8) ◽

pp. 1092-1097 ◽

Cited By ~ 31

Author(s):

Rajaa Alsanea ◽

Sriram Ravindran ◽

Mohamed I. Fayad ◽

Bradford R. Johnson ◽

Christopher S. Wenckus ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Pulp Stem Cells ◽

Dentin Matrix Protein 1 ◽

Dentin Matrix Protein ◽

Dentin Matrix ◽

Biomimetic Approach

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Upregulation of dentin matrix protein 1 promoter activities by core binding factor α1 in human dental pulp stem cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.03.188 ◽

2007 ◽

Vol 357 (2) ◽

pp. 505-510 ◽

Cited By ~ 7

Author(s):

Jianliang Pang ◽

Yaqing Zhang ◽

Jie Ke ◽

Qing Yu ◽

Wenxi He ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Pulp Stem Cells ◽

Dentin Matrix Protein 1 ◽

Core Binding Factor ◽

Dentin Matrix Protein ◽

Binding Factor ◽

Human Dental Pulp ◽

Dentin Matrix

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Deferoxamine-Induced Migration and Odontoblast Differentiation via ROS-Dependent Autophagy in Dental Pulp Stem Cells

Cellular Physiology and Biochemistry ◽

10.1159/000484506 ◽

2017 ◽

Vol 43 (6) ◽

pp. 2535-2547 ◽

Cited By ~ 9

Author(s):

Xuan Wang ◽

Tian Tian Wu ◽

Long Jiang ◽

Du Rong ◽

Ya Qin Zhu

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

B Cell Lymphoma ◽

Dental Pulp Stem Cells ◽

Dependent Manner ◽

Alizarin Red ◽

Odontoblast Differentiation ◽

Alkaline Phosphatase Staining ◽

Autophagic Activity ◽

Autophagy Inhibition

Background/Aims: As a vital degradation and recycling system, autophagy plays an essential role in regulating the differentiation of stem cells. We previously showed that iron chelator deferoxamine (DFO) could promote the repair ability of dental pulp stem cells (DPSCs). Here, we investigated the effect of DFO in autophagy and the role of autophagy in regulating the migration and odontoblast differentiation of DPSCs. Methods: Transmission electron microscopy, immunofluorescence staining and western blotting were performed to evaluate the autophagic activity of DPSCs. Transmigration assay, alkaline phosphatase staining/activity, alizarin red S staining and quantitative PCR were performed to examine the migration and odontoblast differentiation of DPSCs. Reactive oxygen species (ROS) levels and the effects of ROS scavenger in autophagy induction were also detected. Autophagy inhibitors (3-MA and bafilomycin A1) and lentiviral vectors carrying ATG5 shRNA sequences were used for autophagy inhibition. Results: Early exposure to DFO promoted the mineralization of DPSCs and increased autophagic activity. Autophagy inhibition suppressed DFO-induced DPSC migration and odontoblast differentiation. Furthermore, DFO treatment could induce autophagy partly through hypoxia-inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K-interacting protein 3 (HIF-1α/BNIP3) pathway in a ROS-dependent manner. Conclusion: DFO increased DPSC migration and differentiation, which might be modulated through ROS-induced autophagy.

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Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts

Gene Therapy ◽

10.1038/sj.gt.3302687 ◽

2005 ◽

Vol 13 (7) ◽

pp. 611-620 ◽

Cited By ~ 135

Author(s):

A Almushayt ◽

K Narayanan ◽

A E Zaki ◽

A George

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Pulp Stem Cells ◽

Dentin Matrix Protein 1 ◽

Dentin Matrix Protein ◽

Dentin Matrix

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In Vivo Generation of Dental Pulp-like Tissue by Using Dental Pulp Stem Cells, a Collagen Scaffold, and Dentin Matrix Protein 1 after Subcutaneous Transplantation in Mice

Journal of Endodontics ◽

10.1016/j.joen.2008.02.005 ◽

2008 ◽

Vol 34 (4) ◽

pp. 421-426 ◽

Cited By ~ 167

Author(s):

Rebecca S. Prescott ◽

Rajaa Alsanea ◽

Mohamed I. Fayad ◽

Bradford R. Johnson ◽

Christopher S. Wenckus ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Collagen Scaffold ◽

Dental Pulp Stem Cells ◽

Dentin Matrix Protein 1 ◽

Dentin Matrix Protein ◽

Subcutaneous Transplantation ◽

Dentin Matrix

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Enhanced Osteogenesis of Dental Pulp Stem Cells In Vitro Induced by Chitosan–PEG-Incorporated Calcium Phosphate Cement

Polymers ◽

10.3390/polym13142252 ◽

2021 ◽

Vol 13 (14) ◽

pp. 2252

Author(s):

Jae Eun Kim ◽

Sangbae Park ◽

Woong-Sup Lee ◽

Jinsub Han ◽

Jae Woon Lim ◽

...

Keyword(s):

Stem Cells ◽

Calcium Phosphate ◽

Zeta Potential ◽

Mechanical Strength ◽

Calcium Phosphate Cement ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Ion Trapping ◽

Alizarin Red

The use of bone graft materials is required for the treatment of bone defects damaged beyond the critical defect; therefore, injectable calcium phosphate cement (CPC) is actively used after surgery. The application of various polymers to improve injectability, mechanical strength, and biological function of injection-type CPC is encouraged. We previously developed a chitosan–PEG conjugate (CS/PEG) by a sulfur (VI) fluoride exchange reaction, and the resulting chitosan derivative showed high solubility at a neutral pH. We have demonstrated the CPC incorporated with a poly (ethylene glycol) (PEG)-grafted chitosan (CS/PEG) and developed CS/PEG CPC. The characterization of CS/PEG CPC was conducted using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The initial properties of CS/PEG CPCs, such as the pH, porosity, mechanical strength, zeta potential, and in vitro biocompatibility using the WST-1 assay, were also investigated. Moreover, osteocompatibility of CS/PEG CPCs was carried out via Alizarin Red S staining, immunocytochemistry, and Western blot analysis. CS/PEG CPC has enhanced mechanical strength compared to CPC, and the cohesion test also demonstrated in vivo stability. Furthermore, we determined whether CS/PEG CPC is a suitable candidate for promoting the osteogenic ability of Dental Pulp Stem Cells (DPSC). The elution of CS/PEG CPC entraps more calcium ion than CPC, as confirmed through the zeta potential test. Accordingly, the ion trapping effect of CS/PEG is considered to have played a role in promoting osteogenic differentiation of DPSCs. The results strongly suggested that CS/PEG could be used as suitable additives for improving osteogenic induction of bone substitute materials.

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Hypoxia-inducible factor 1α induces osteo/odontoblast differentiation of human dental pulp stem cells via Wnt/β-catenin transcriptional cofactor BCL9

Scientific Reports ◽

10.1038/s41598-021-04453-8 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Shion Orikasa ◽

Nobuyuki Kawashima ◽

Kento Tazawa ◽

Kentaro Hashimoto ◽

Keisuke Sunada-Nara ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Target Genes ◽

Hypoxia Inducible Factor ◽

Dental Pulp Stem Cells ◽

Pulp Tissue ◽

Odontoblast Differentiation ◽

Hypoxia Inducible Factor 1Α ◽

Hypoxic Conditions

AbstractAccelerated dental pulp mineralization is a common complication in avulsed/luxated teeth, although the mechanisms underlying this remain unclear. We hypothesized that hypoxia due to vascular severance may induce osteo/odontoblast differentiation of dental pulp stem cells (DPSCs). This study examined the role of B-cell CLL/lymphoma 9 (BCL9), which is downstream of hypoxia-inducible factor 1α (HIF1α) and a Wnt/β-catenin transcriptional cofactor, in the osteo/odontoblastic differentiation of human DPSCs (hDPSCs) under hypoxic conditions. hDPSCs were isolated from extracted healthy wisdom teeth. Hypoxic conditions and HIF1α overexpression induced significant upregulation of mRNAs for osteo/odontoblast markers (RUNX2, ALP, OC), BCL9, and Wnt/β-catenin signaling target genes (AXIN2, TCF1) in hDPSCs. Overexpression and suppression of BCL9 in hDPSCs up- and downregulated, respectively, the mRNAs for AXIN2, TCF1, and the osteo/odontoblast markers. Hypoxic-cultured mouse pulp tissue explants showed the promotion of HIF1α, BCL9, and β-catenin expression and BCL9-β-catenin co-localization. In addition, BCL9 formed a complex with β-catenin in hDPSCs in vitro. This study demonstrated that hypoxia/HIF1α-induced osteo/odontoblast differentiation of hDPSCs was partially dependent on Wnt/β-catenin signaling, where BCL9 acted as a key mediator between HIF1α and Wnt/β-catenin signaling. These findings may reveal part of the mechanisms of dental pulp mineralization after traumatic dental injury.

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Dental pulp stem cells: Potential significance in regenerative medicine

Stomatoloski glasnik Srbije ◽

10.2298/sgs0803170t ◽

2008 ◽

Vol 55 (3) ◽

pp. 170-179 ◽

Cited By ~ 5

Author(s):

Vera Todorovic ◽

Dejan Markovic ◽

Nadezda Milosevic-Jovcic ◽

Marijana Petakov ◽

Bela Balint ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Pulp Stem Cells ◽

Deciduous Teeth ◽

High Plasticity ◽

Dental Stem Cells ◽

Periodontal Tissues ◽

Extracellular Matrix Components

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.

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