Genipin, a Cross-linking Agent, Promotes Odontogenic Differentiation of Human Dental Pulp Cells

Kwon, Yong-Ju; Lim, Eun-Su; Kim, Hye-Min; Hwang, Yun-Chan; Lee, Kwang Won; Min, Kyung-San

doi:10.1016/j.joen.2014.12.002

Cited by 42 publications

(35 citation statements)

References 39 publications

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“…The increased proliferation of hPDLCs may be due to the enhanced physical properties demonstrated in our current study. Furthermore, these findings are supported by several previous studies which showed that the crosslinking of collagen leads to an improvement in cell adhesion and proliferation 1718203233. When counting cells, DAPI staining was used to help distinguish cells from the collagen substrate.…”

Section: Discussionsupporting

confidence: 73%

Effects of proanthocyanidin, a crosslinking agent, on physical and biological properties of collagen hydrogel scaffold

2016

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ObjectivesThe purpose of the present study was to evaluate the effects of proanthocyanidin (PAC), a crosslinking agent, on the physical properties of a collagen hydrogel and the behavior of human periodontal ligament cells (hPDLCs) cultured in the scaffold.Materials and MethodsViability of hPDLCs treated with PAC was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The physical properties of PAC treated collagen hydrogel scaffold were evaluated by the measurement of setting time, surface roughness, and differential scanning calorimetry (DSC). The behavior of the hPDLCs in the collagen scaffold was evaluated by cell morphology observation and cell numbers counting.ResultsThe setting time of the collagen scaffold was shortened in the presence of PAC (p < 0.05). The surface roughness of the PAC-treated collagen was higher compared to the untreated control group (p < 0.05). The thermogram of the crosslinked collagen exhibited a higher endothermic peak compared to the uncrosslinked one. Cells in the PAC-treated collagen were observed to attach in closer proximity to one another with more cytoplasmic extensions compared to cells in the untreated control group. The number of cells cultured in the PAC-treated collagen scaffolds was significantly increased compared to the untreated control (p < 0.05).ConclusionsOur results showed that PAC enhanced the physical properties of the collagen scaffold. Furthermore, the proliferation of hPDLCs cultured in the collagen scaffold crosslinked with PAC was facilitated. Conclusively, the application of PAC to the collagen scaffold may be beneficial for engineering-based periodontal ligament regeneration in delayed replantation.

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Section: Discussionsupporting

confidence: 73%

Effects of proanthocyanidin, a crosslinking agent, on physical and biological properties of collagen hydrogel scaffold

2016

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“…The collagen scaffold was prepared by using the method described previously 13 . Briefly, a purified bovine collagen solution (PurCol; Advanced BioMatrix Inc., Tucson, AZ, USA) and 10×PBS were mixed in an 8:1 ratio and adjusted to a pH of 7.4 with 1 mL of sodium hydroxide (1 M) (Bio Basic Canada Inc., Markham, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

Effects of epicatechin, a crosslinking agent, on human dental pulp cells cultured in collagen scaffolds

Lim

Min

et al. 2016

J. Appl. Oral Sci.

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Objective The purpose of this study was to investigate the biological effects of epicatechin (ECN), a crosslinking agent, on human dental pulp cells (hDPCs) cultured in collagen scaffolds.Material and Method To evaluate the effects of ECN on the proliferation of hDPCs, cell counting was performed using optical and fluorescent microscopy. Measurements of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time polymerase chain reactions were performed to assess odontogenic differentiation. The compressive strength and setting time of collagen scaffolds containing ECN were measured. Differential scanning calorimetry was performed to analyze the thermal behavior of collagen in the presence of ECN.Results Epicatechin increased ALP activity, mineralized nodule formation, and the mRNA expression of dentin sialophosphoprotein (DSPP), a specific odontogenic-related marker. Furthermore, ECN upregulated the expression of DSPP in hDPCs cultured in collagen scaffolds. Epicatechin activated the extracellular signal-regulated kinase (ERK) and the treatment with an ERK inhibitor (U0126) blocked the expression of DSPP. The compressive strength was increased and the setting time was shortened in a dose-dependent manner. The number of cells cultured in the ECN-treated collagen scaffolds was significantly increased compared to the cells in the untreated control group.Conclusions Our results revealed that ECN promoted the proliferation and differentiation of hDPCs. Furthermore, the differentiation was regulated by the ERK signaling pathway. Changes in mechanical properties are related to cell fate, including proliferation and differentiation. Therefore, our study suggests the ECN treatment might be desirable for dentin-pulp complex regeneration.

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“…Aubeux et al (2016) reported that silated-hydroxypropyl methylcellulose used as a hydrogel scaffold was also able to extract dentine matrix proteins from dentine powder. Additionally, other molecules have been suggested as potential stimulators for odontogenic differentiation from human dental pulp cells, such as a natural collagen cross-linking agent genipin, that could also improve physical properties of collagen scaffolds (Kwon et al 2015), an actin-severing and actin-capping protein called adseverin (Li et al 2015), and Nell-like molecule-1 (Nell-1) (Liu et al 2016). Strategies to clinically translate our biological understanding of pulp regeneration into improved patient management approaches could overcome the shortcomings of biomaterials available on the market at present (Simon & Smith 2014).…”

Section: Current Challenges and Future Directionsmentioning

confidence: 99%

Disclosing the physiology of pulp tissue for vital pulp therapy

2018

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The discovery that dentine is a reservoir of bioactive molecules that can be recruited on demand has attracted efforts to develop new protocols and materials for vital pulp therapy (VPT). The noncollagenous proteins (NCPs) present in the dentine extracellular matrix (ECM) include growth factors (TGF-β1, BMP-7, FGF-2, IGF-1 and IGF-2, NGF and GDNF), extracellular matrix molecules (DSP, DPP, BSP, DMP-1 and DSPP) and both anti-inflammatory and pro-inflammatory chemokines and cytokines (TNF-α, IL-1, IL-6 and IL-10). Molecules such as DSP and DPP are mainly expressed by odontoblasts, and they are cleaved products from dentine sialophosphoprotein (DSPP). Some molecules, such as TGF-β1, specifically interact with decorin/biglycan in dentine. Although TGF-β1 increases the expression and secretion of NGF in human pulp cells, NGF induces mineralization and increases the expression of DSPP and DMP-1. Furthermore, GDNF may act as a cell survival factor and mitogen during tooth injury and repair. Pulp capping materials, such as MTA and calcium hydroxide, can solubilize bioactive dentine molecules (TGF-β1, NGF and GDNF) that stimulate tertiary dentinogenesis. The binding of these signalling molecules leads to activation of several signalling transduction pathways involved in dentinogenesis, odontoblast differentiation and inflammatory responses, such as the p38 MAPK, NF-kβ and Wnt/β-catenin signalling pathways. Understanding the cascade of cellular and molecular events underlying the repair and regeneration processes provides a reasonable new approach to VPT through a targeted interaction between tooth tissue and bioactive molecules.

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Genipin, a Cross-linking Agent, Promotes Odontogenic Differentiation of Human Dental Pulp Cells

Cited by 42 publications

References 39 publications

Effects of proanthocyanidin, a crosslinking agent, on physical and biological properties of collagen hydrogel scaffold

Effects of proanthocyanidin, a crosslinking agent, on physical and biological properties of collagen hydrogel scaffold

Effects of epicatechin, a crosslinking agent, on human dental pulp cells cultured in collagen scaffolds

Disclosing the physiology of pulp tissue for vital pulp therapy

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