scholarly journals Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury

2018 ◽  
Vol 97 (9) ◽  
pp. 1047-1054 ◽  
Author(s):  
Y. Zhao ◽  
X. Yuan ◽  
B. Liu ◽  
U.S. Tulu ◽  
J.A. Helms
Keyword(s):  
Wnt Signaling ◽  
Proof Of Concept ◽  
Pulp Tissue ◽  
Dentinal Tubules ◽  
Acute Trauma ◽  
Injury Model ◽  
Pulp Exposure ◽  
Pulp Cells ◽  
Dentin Formation ◽  
Pulp Repair

The objective of our experiments was to identify new therapeutic strategies to stimulate dentin formation in an adult tooth. To address this objective, we evaluated dentin production in 2 acute trauma models: one involving a pulp exposure and the other involving a superficial dentin injury. Molecular, cellular, and histologic analyses revealed that in response to a severe injury, where the pulp is exposed to the oral cavity, cell death is rampant and the repair response initiates from surviving pulp cells and, to a lesser extent, surviving odontoblasts. When an injury is superficial, as in the case of a dentin injury model, then disturbances are largely confined to pulp tissue immediately underneath the damaged dentin tubules. We found that the pulp remained vital and innervated; primary odontoblasts upregulated HIF1α; and the rate of mineralization was significantly increased. A tamoxifen-inducible Axin2CreERT2/+; R26R mTmG/+ reporter strain was then used to demonstrate that a population of long-lived Wnt-responsive odontoblasts, which secreted dentin throughout the life of the animal, were responsible for depositing new dentin in response to a superficial injury. Amplifying Wnt signaling in the pulp stimulates dentin secretion, and in the dentin injury model, we show that a liposomal formulation of human WNT3A protein passes through dentinal tubules and is capable of upregulating Wnt signaling in the pulp. These data provide strong proof of concept for a therapeutic pulp-capping material to stimulate Wnt signaling in odontoblasts and thus improve the pulp repair response.

scholarly journals Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Chen ◽  
Huaxing Xu ◽  
Kun Xia ◽  
Shuhua Cheng ◽  
Qi Zhang
Keyword(s):  
Dental Pulp ◽  
Tissue Repair ◽  
Pulp Tissue ◽  
Tissue Repair And Regeneration ◽  
Injury Model ◽  
Tnf Α ◽  
Pulp Inflammation ◽  
Inflammation Resolution ◽  
Pulp Repair ◽  
Dentin Regeneration

Abstract Background Unresolved inflammation and tissue destruction are considered to underlie the failure of dental pulp repair. As key mediators of the injury response, dental pulp stem cells (DPSCs) play a critical role in pulp tissue repair and regeneration. Resolvin E1 (RvE1), a major dietary omega-3 polyunsaturated fatty-acid metabolite, is effective in resolving inflammation and activating wound healing. However, whether RvE1 facilitates injured pulp-tissue repair and regeneration through timely resolution of inflammation and rapid mobilization of DPSCs is unknown. Therefore, we established a pulp injury model and investigated the effects of RvE1 on DPSC-mediated inflammation resolution and injured pulp repair. Methods A pulp injury model was established using 8-week-old Sprague-Dawley rats. Animals were sacrificed on days 1, 3, 7, 14, 21, and 28 after pulp capping with a collagen sponge immersed in PBS with RvE1 or PBS. Hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry, and immunohistofluorescence were used to evaluate the prohealing properties of RvE1. hDPSCs were incubated with lipopolysaccharide (LPS) to induce an inflammatory response, and the expression of inflammatory factors after RvE1 application was measured. Effects of RvE1 on hDPSC proliferation, chemotaxis, and odontogenic differentiation were evaluated by CCK-8 assay, transwell assay, alkaline phosphatase (ALP) staining, alizarin red staining, and quantitative PCR, and possible signaling pathways were explored using western blotting. Results In vivo, RvE1 reduced the necrosis rate of damaged pulp and preserved more vital pulps, and promoted injured pulp repair and reparative dentin formation. Further, it enhanced dentin matrix protein 1 and dentin sialoprotein expression and accelerated pulp inflammation resolution by suppressing TNF-α and IL-1β expression. RvE1 enhanced the recruitment of CD146+ and CD105+ DPSCs to the damaged molar pulp mesenchyme. Isolated primary cells exhibited the mesenchymal stem cell immunophenotype and differentiation. RvE1 promoted hDPSC proliferation and chemotaxis. RvE1 significantly attenuated pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and enhanced ALP activity, nodule mineralization, and especially, expression of the odontogenesis-related genes DMP1, DSPP, and BSP in LPS-stimulated DPSCs. RvE1 regulated AKT, ERK, and rS6 phosphorylation in LPS-stimulated DPSCs. Conclusions RvE1 promotes pulp inflammation resolution and dentin regeneration and positively influences the proliferation, chemotaxis, and differentiation of LPS-stimulated hDPSCs. This response is, at least partially, dependent on AKT, ERK, and rS6-associated signaling in the inflammatory microenvironment. RvE1 has promising application potential in regenerative endodontics.

scholarly journals Translation Approach for Dentine Regeneration Using GSK-3 Antagonists

2020 ◽  
Vol 99 (5) ◽  
pp. 544-551 ◽  
Author(s):  
L.K. Zaugg ◽  
A. Banu ◽  
A.R. Walther ◽  
D. Chandrasekaran ◽  
R.C. Babb ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Pulp Tissue ◽  
Drug Induced ◽  
Simple Method ◽  
Pulp Exposure ◽  
Pulp Cells ◽  
Noncompetitive Inhibitor ◽  
Canonical Wnt ◽  
Direct Capping ◽  
Rat Molars

The canonical Wnt/β-catenin signaling pathway is crucial for reparative dentinogenesis following tooth damage, and the modulation of this pathway affects the rate and extent of reparative dentine formation in damaged mice molars by triggering the natural process of dentinogenesis. Pharmacological stimulation of Wnt/β-catenin signaling activity by small-molecule GSK-3 inhibitor drugs following pulp exposure in mouse molars results in reparative dentinogenesis. The creation of similar but larger lesions in rat molars shows that the adenosine triphosphate (ATP)–competitive GSK-3 inhibitor, CHIR99021 (CHIR), and the ATP noncompetitive inhibitor, Tideglusib (TG), can equally enhance reparative dentine formation to fully repair an area of dentine damage up to 10 times larger, mimicking the size of small lesions in humans. To assess the chemical composition of this newly formed dentine and to compare its structure with surrounding native dentine and alveolar bone, Raman microspectroscopy analysis is used. We show that the newly formed dentine comprises equal carbonate to phosphate ratios and mineral to matrix ratios to that of native dentine, both being significantly different from bone. For an effective dentine repair, the activity of the drugs needs to be restricted to the region of damage. To investigate the range of drug-induced Wnt-activity within the dental pulp, RNA of short-term induced (24-h) molars is extracted from separated roots and crowns, and quantitative Axin2 expression is assayed. We show that the activation of Wnt/β-catenin signaling is highly restricted to pulp cells in the immediate location of the damage in the coronal pulp tissue with no drug action detected in the root pulp. These results provide further evidence that this simple method of enhancement of natural reparative dentinogenesis has the potential to be translated into a clinical direct capping approach.

scholarly journals Tenascin and Fibronectin Expression after Pulp Capping with Different Hemostatic Agents: A Preliminary Study

2013 ◽  
Vol 24 (3) ◽  
pp. 188-193 ◽  
Author(s):  
Elaine Zanchin Baldissera ◽  
Adriana Fernandes da Silva ◽  
Ana Paula Neutzling Gomes ◽  
Adriana Etges ◽  
Tatiana Botero ◽  
...  
Keyword(s):  
Pulp Tissue ◽  
Variable Expression ◽  
Hemostatic Agents ◽  
Exposure Site ◽  
Reparative Dentin ◽  
Fibronectin Expression ◽  
Mineralized Tissues ◽  
Pulp Exposure ◽  
Positive Immunostaining ◽  
Pulp Repair

This study investigated the expression of extracellular matrix glycoproteins tenascin (TN) and fibronectin (FN) in pulp repair after capping with calcium hydroxide (CH), following different hemostasis protocols. Class I cavities with a pulp exposure were prepared in 42 human third molars scheduled for extraction. Different hemostatic agents (0.9% saline solution, 5.25% sodium hypochlorite and 2% chlorhexidine digluconate) were used and pulps were capped with CH cement. After 7, 30 or 90 days, teeth were extracted, formalin-fixed, and prepared for immunohistochemical technique. Hemostatic agents did not influence the expression of TN and FN. Both glycoproteins were found in the entire the pulp tissue and around collagen fibers, but were absent in the mineralized tissues. In the predentin, TN showed positive immunostaining and FN had a variable expression. Within 7 days post-treatment, a slightly more pronounced immunostaining on the pulp exposure site was observed. Within 30 days, TN and FN demonstrated a positive expression around the dentin barrier and at 90 days, a thin and linear expression of TN and FN was delimitating the reparative dentin. In conclusion, hemostatic agents did not influence TN and FN expression. Immunostaining for TN and FN was seen in different regions and periods, demonstrating their role in pulp repair.

scholarly journals Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells

2020 ◽  
Author(s):  
Jie Chen ◽  
Huaxing Xu ◽  
Kun Xia ◽  
Shuhua Cheng ◽  
Qi Zhang
Keyword(s):  
Dental Pulp ◽  
Tissue Repair ◽  
Pulp Tissue ◽  
Tissue Repair And Regeneration ◽  
Injury Model ◽  
Tnf Α ◽  
Pulp Inflammation ◽  
Inflammation Resolution ◽  
Pulp Repair ◽  
Dentin Regeneration

Abstract Background Unresolved inflammation and tissue destruction are considered to underlie failure of dental pulp repair. As key mediators of the injury response, dental pulp stem cells (DPSCs) play a critical role in pulp tissue repair and regeneration. Resolvin E1 (RvE1), a major dietary omega-3 polyunsaturated fatty-acid metabolite, is effective in resolving inflammation and activating wound healing. However, whether RvE1 facilitates injured pulp-tissue repair and regeneration through timely resolution of inflammation and rapid mobilization of DPSCs is unknown. Therefore, we established a pulp injury model and investigated the effects of RvE1 on DPSC-mediated inflammation resolution and injured pulp repair. Methods A pulp injury model was established using eight-week-old Sprague-Dawley rats. Animals were sacrificed on days 1, 3, 7, 14, 21, and 28 after pulp capping with a collagen sponge immersed in PBS with RvE1 or PBS. Hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry, and immunohistofluorescence were used to evaluate the prohealing properties of RvE1. hDPSCs were incubated with lipopolysaccharide (LPS) to induce an inflammatory response, and the expression of inflammatory factors after RvE1 application was measured. Effects of RvE1 on hDPSC proliferation, chemotaxis, and odontogenic differentiation were evaluated by CCK-8 assay, transwell assay, alkaline phosphatase (ALP) staining, alizarin red staining, and quantitative PCR, and possible signaling pathways were explored using western blotting. Results In vivo, RvE1 promoted injured pulp repair and reparative dentin formation. Further, it enhanced dentin sialoprotein and nestin expression and accelerated pulp inflammation resolution by suppressing TNF-α and CD68 expression. RvE1 enhanced the recruitment of CD146+ and CD105+ DPSCs to the damaged molar pulp mesenchyme. Isolated primary cells exhibited the mesenchymal stem cell immunophenotype and differentiation. RvE1 promoted hDPSC proliferation and chemotaxis. RvE1 significantly attenuated pro-inflammatory cytokine (TNF-α, CD68, IL-6, and IL-1β) release and enhanced ALP activity, nodule mineralization, and especially, expression of the odontogenesis-related genes DMP-1, DSPP, and BSP in LPS-stimulated DPSCs. RvE1 regulated Akt, ERK, and rS6 phosphorylation. Conclusions RvE1 promotes pulp inflammation resolution and dentin regeneration and positively influences the proliferation, chemotaxis, and differentiation of LPS-stimulated hDPSCs. This response is, at least partially, dependent on Akt, ERK, and rS6-associated signaling. RvE1 has promising application potential in regenerative endodontics.

scholarly journals Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells

2020 ◽  
Author(s):  
Jie Chen ◽  
Huaxing Xu ◽  
Kun Xia ◽  
Shuhua Cheng ◽  
Qi Zhang
Keyword(s):  
Dental Pulp ◽  
Tissue Repair ◽  
Pulp Tissue ◽  
Tissue Repair And Regeneration ◽  
Injury Model ◽  
Tnf Α ◽  
Pulp Inflammation ◽  
Inflammation Resolution ◽  
Pulp Repair ◽  
Dentin Regeneration

Abstract Background: Unresolved inflammation and tissue destruction are considered to underlie failure of dental pulp repair. As key mediators of the injury response, dental pulp stem cells (DPSCs) play a critical role in pulp tissue repair and regeneration. Resolvin E1 (RvE1), a major dietary omega-3 polyunsaturated fatty-acid metabolite, is effective in resolving inflammation and activating wound healing. However, whether RvE1 facilitates injured pulp-tissue repair and regeneration through timely resolution of inflammation and rapid mobilization of DPSCs is unknown. Therefore, we established a pulp injury model and investigated the effects of RvE1 on DPSC-mediated inflammation resolution and injured pulp repair.Methods: A pulp injury model was established using eight-week-old Sprague-Dawley rats. Animals were sacrificed on days 1, 3, 7, 14, 21, and 28 after pulp capping with a collagen sponge immersed in PBS with RvE1 or PBS. Hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry, and immunohistofluorescence were used to evaluate the prohealing properties of RvE1. hDPSCs were incubated with lipopolysaccharide (LPS) to induce an inflammatory response, and the expression of inflammatory factors after RvE1 application was measured. Effects of RvE1 on hDPSC proliferation, chemotaxis, and odontogenic differentiation were evaluated by CCK-8 assay, transwell assay, alkaline phosphatase (ALP) staining, alizarin red staining, and quantitative PCR, and possible signaling pathways were explored using western blotting.Results: In vivo, RvE1 promoted injured pulp repair and reparative dentin formation. Further, it enhanced dentin sialoprotein expression and accelerated pulp inflammation resolution by suppressing TNF-α and IL-1β expression. RvE1 enhanced the recruitment of CD146+ and CD105+ DPSCs to the damaged molar pulp mesenchyme. Isolated primary cells exhibited the mesenchymal stem cell immunophenotype and differentiation. RvE1 promoted hDPSC proliferation and chemotaxis. RvE1 significantly attenuated pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and enhanced ALP activity, nodule mineralization, and especially, expression of the odontogenesis-related genes DMP-1, DSPP, and BSP in LPS-stimulated DPSCs. RvE1 regulated Akt, ERK, and rS6 phosphorylation in LPS-stimulated DPSCs.Conclusions: RvE1 promotes pulp inflammation resolution and dentin regeneration and positively influences the proliferation, chemotaxis, and differentiation of LPS-stimulated hDPSCs. This response is, at least partially, dependent on Akt, ERK, and rS6-associated signaling in the inflammatory microenvironment. RvE1 has promising application potential in regenerative endodontics.

scholarly journals Resolvin E1 accelerates pulp repair by regulating inflammation and stimulating dentin regeneration in dental pulp stem cells

2020 ◽  
Author(s):  
Jie Chen ◽  
Huaxing Xu ◽  
Kun Xia ◽  
Shuhua Cheng ◽  
Qi Zhang
Keyword(s):  
Dental Pulp ◽  
Tissue Repair ◽  
Pulp Tissue ◽  
Tissue Repair And Regeneration ◽  
Injury Model ◽  
Tnf Α ◽  
Pulp Inflammation ◽  
Inflammation Resolution ◽  
Pulp Repair ◽  
Dentin Regeneration

Abstract Background: Unresolved inflammation and tissue destruction are considered to underlie failure of dental pulp repair. As key mediators of the injury response, dental pulp stem cells (DPSCs) play a critical role in pulp tissue repair and regeneration. Resolvin E1 (RvE1), a major dietary omega-3 polyunsaturated fatty-acid metabolite, is effective in resolving inflammation and activating wound healing. However, whether RvE1 facilitates injured pulp-tissue repair and regeneration through timely resolution of inflammation and rapid mobilization of DPSCs is unknown. Therefore, we established a pulp injury model and investigated the effects of RvE1 on DPSC-mediated inflammation resolution and injured pulp repair.Methods: A pulp injury model was established using eight-week-old Sprague-Dawley rats. Animals were sacrificed on days 1, 3, 7, 14, 21, and 28 after pulp capping with a collagen sponge immersed in PBS with RvE1 or PBS. Hematoxylin-eosin and Masson’s trichrome staining, immunohistochemistry, and immunohistofluorescence were used to evaluate the prohealing properties of RvE1. hDPSCs were incubated with lipopolysaccharide (LPS) to induce an inflammatory response, and the expression of inflammatory factors after RvE1 application was measured. Effects of RvE1 on hDPSC proliferation, chemotaxis, and odontogenic differentiation were evaluated by CCK-8 assay, transwell assay, alkaline phosphatase (ALP) staining, alizarin red staining, and quantitative PCR, and possible signaling pathways were explored using western blotting.Results: In vivo, RvE1 reduced the necrosis rate of damaged pulp and preserved more vital pulp, promoted injured pulp repair and reparative dentin formation. Further, it enhanced dentin matrix protein 1 and dentin sialoprotein expression, and accelerated pulp inflammation resolution by suppressing TNF-α and IL-1β expression. RvE1 enhanced the recruitment of CD146+ and CD105+ DPSCs to the damaged molar pulp mesenchyme. Isolated primary cells exhibited the mesenchymal stem cell immunophenotype and differentiation. RvE1 promoted hDPSC proliferation and chemotaxis. RvE1 significantly attenuated pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) release and enhanced ALP activity, nodule mineralization, and especially, expression of the odontogenesis-related genes DMP1, DSPP, and BSP in LPS-stimulated DPSCs. RvE1 regulated AKT, ERK, and rS6 phosphorylation in LPS-stimulated DPSCs.Conclusions: RvE1 promotes pulp inflammation resolution and dentin regeneration and positively influences the proliferation, chemotaxis, and differentiation of LPS-stimulated hDPSCs. This response is, at least partially, dependent on AKT, ERK, and rS6-associated signaling in the inflammatory microenvironment. RvE1 has promising application potential in regenerative endodontics.

Effect of a Calcium-silicate-based Restorative Cement on Pulp Repair

2012 ◽  
Vol 91 (12) ◽  
pp. 1166-1171 ◽  
Author(s):  
X.V. Tran ◽  
C. Gorin ◽  
C. Willig ◽  
B. Baroukh ◽  
B. Pellat ◽  
...  
Keyword(s):  
Calcium Silicate ◽  
Glass Ionomer Cement ◽  
Repair Process ◽  
Male Rats ◽  
Time Points ◽  
Tertiary Dentin ◽  
Pulp Exposure ◽  
Calcium Silicate Cements ◽  
Reparative Process ◽  
Dentin Formation

In cases of pulp injury, capping materials are used to enhance tertiary dentin formation; Ca(OH)2 and MTA are the current gold standards. The aim of this study was to evaluate the capacity of a new calcium-silicate-based restorative cement to induce pulp healing in a rat pulp injury model. For that purpose, cavities with mechanical pulp exposure were prepared on maxillary first molars of 27 six-week-old male rats, and damaged pulps were capped with either the new calcium-silicate-based restorative cement (Biodentine), MTA, or Ca(OH)2. Cavities were sealed with glass-ionomer cement, and the repair process was assessed at several time-points. At day 7, our results showed that both the evaluated cement and MTA induced cell proliferation and formation of mineralization foci, which were strongly positive for osteopontin. At longer time-points, we observed the formation of a homogeneous dentin bridge at the injury site, secreted by cells displaying an odontoblastic phenotype. In contrast, the reparative tissue induced by Ca(OH)2 showed porous organization, suggesting a reparative process different from those induced by calcium silicate cements. Analysis of these data suggests that the evaluated cement can be used for direct pulp-capping.

FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model

2018 ◽  
Vol 37 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Ken Sugiyama ◽  
Kosuke Nagashima ◽  
Takahiro Miwa ◽  
Yuta Shimizu ◽  
Tomoko Kawaguchi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dental Pulp ◽  
Dental Pulp Cells ◽  
Rat Spinal Cord ◽  
Human Dental Pulp Cells ◽  
Spinal Cord Injury Model ◽  
Injury Model ◽  
Cord Injury ◽  
Human Dental Pulp ◽  
Pulp Cells

Regeneration of dental pulp tissue in immature teeth with apical periodontitis using platelet-rich plasma and dental pulp cells

2013 ◽  
Vol 46 (10) ◽  
pp. 962-970 ◽  
Author(s):  
W. Zhu ◽  
X. Zhu ◽  
G. T.-J. Huang ◽  
G. S. P. Cheung ◽  
W. L. Dissanayaka ◽  
...  
Keyword(s):  
Dental Pulp ◽  
Platelet Rich Plasma ◽  
Apical Periodontitis ◽  
Dental Pulp Cells ◽  
Pulp Tissue ◽  
Immature Teeth ◽  
Dental Pulp Tissue ◽  
Pulp Cells

scholarly journals Induction of reparative dentin by calcium silicate-based material as direct pulp capping agent

2019 ◽  
Vol 12 (4) ◽  
pp. 182-186
Author(s):  
Mozammal Hossain ◽  
Mahmood Sajedeen ◽  
Yukio Nakamura
Keyword(s):  
Calcium Hydroxide ◽  
Calcium Silicate ◽  
Normal Function ◽  
Direct Pulp Capping ◽  
Pulp Tissue ◽  
Pulp Capping ◽  
Exposure Site ◽  
Reparative Dentin ◽  
Dentin Formation ◽  
Reparative Dentin Formation

This study was performed to examine whether calcium silicate could induce reparative dentin formation without eliciting any adverse effect in direct pulp capping of premolar teeth. Twenty participants who need extraction of their 4 healthy permanent premolar teeth for orthodontic reasons were included in this study. Following the surgical procedure, the exposed pulp tissue was treated either with calcium silicate or covered with calcium hydroxide paste. On day 3, 7, 14 and 28, the experimental teeth was extracted and examined using light microscopy and histometric analysis to observe the inflammatory changes and the amount of reparative dentin formation. The results showed that in the calcium silicate treated teeth, substantial amounts of dentine-like tissue was formed on day 14 and mostly located on the exposure site. It was also observed in the calcium hydroxide treated teeth but dentin-like tissue located at a distance from the exposure site. The total amount of reparative dentine formed in the calcium silicate-treated teeth was significantly higher (p<0.005) than in the calcium hydroxide-treated specimens. In conclusion that the calcium silicate indices pulpal wound healing and reparative formation in the exposed teeth without affecting the normal function of the remaining pulp.

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