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 ◽  
...  

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.

2009 ◽  
Vol 3 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Antonio Vinicius Holanda Barbosa ◽  
Gerhilde Callou Sampaio ◽  
Fábio Almeida Gomes ◽  
Daniel Pinto de Oliveira ◽  
Diana Santana de Albuquerque ◽  
...  

This study evaluated the short-term response of human pulp tissue when directly capped with Portland cement. In this series of cases, twenty human third molars that were scheduled for extraction were used. After cavity preparation, pulp exposure was achieved and Portland cement pulp capping was performed. Teeth were extracted after 1, 7, 14 and 21 days following treatment and prepared for histological examination and bacterial detection. Each group had 5 teeth. The results were descriptively analysed. Dentin bridge formation was seen in two teeth with some distance from the material interface (14 and 21 days). Soft inflammatory responses were observed in most of the cases. Bacteria were not disclosed in any specimen. PC exhibited some features of biocompatibility and capability of inducing mineral pulp response in short-term evaluation. The results suggested that PC has a potential to be used as a less expensive pulp capping material in comparison to other pulp capping materials.


2018 ◽  
Vol 97 (9) ◽  
pp. 1047-1054 ◽  
Author(s):  
Y. Zhao ◽  
X. Yuan ◽  
B. Liu ◽  
U.S. Tulu ◽  
J.A. Helms

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.


2010 ◽  
Vol 24 (1) ◽  
pp. 08-14 ◽  
Author(s):  
Alfonso Gala-Garcia ◽  
Karina Imaculada Rosa Teixeira ◽  
Francisco Henrique Lana Wykrota ◽  
Rubén Dario Sinisterra ◽  
Maria Esperanza Cortés

2013 ◽  
Vol 46 (10) ◽  
pp. 962-970 ◽  
Author(s):  
W. Zhu ◽  
X. Zhu ◽  
G. T.-J. Huang ◽  
G. S. P. Cheung ◽  
W. L. Dissanayaka ◽  
...  

Odontology ◽  
2016 ◽  
Vol 105 (4) ◽  
pp. 392-397 ◽  
Author(s):  
Takafumi Ito ◽  
Tomoatsu Kaneko ◽  
Yukiko Sueyama ◽  
Reika Kaneko ◽  
Takashi Okiji

2007 ◽  
Vol 86 (8) ◽  
pp. 780-785 ◽  
Author(s):  
N. Six ◽  
D. Septier ◽  
C. Chaussain-Miller ◽  
R. Blacher ◽  
P. DenBesten ◽  
...  

Phosphorylated extracellular matrix proteins, including matrix extracellular phosphoprotein (MEPE), are involved in the formation and mineralization of dental tissues. In this study, we evaluated the potential of Dentonin, a synthetic peptide derived from MEPE, to promote the formation of reparative dentin. Agarose beads, either soaked with Dentonin or unloaded, were implanted into the pulps of rat molars, and examined 8, 15, and 30 days after treatment. At day 8, Dentonin promoted the proliferation of pulp cells, as visualized by PCNA-labeling. RP59-positive osteoblast progenitors were located around the Dentonin-soaked beads. PCNA- and RP59-labeling were decreased at day 15, while osteopontin, weakly labeled at day 8, was increased at 15 days, but dentin sialoprotein was undetectable at any time. At 8 days, precocious reparative dentin formation occurred in pulps containing Dentonin-soaked beads, with formation slowing after 15 days. These results suggest that Dentonin affects primarily the initial cascade of events leading to pulp healing.


1970 ◽  
Vol 23 (5) ◽  
pp. 1143 ◽  
Author(s):  
CJ Brady ◽  
PBH O'connell ◽  
J Smydzuk ◽  
NL Wade

The permeability of pulp tissue of banana fruits and aseptically prepared transverse slices of bananas increases before the respiratory climacteric begins. The permeability change may be measured as leakage of amino acids from pulp tissue, and is not dependent on the soluble carbohydrate content of pulp cells. During the climacteric, amino acid leakage into water increases further.


Author(s):  
Lívia De Souza Tolentino ◽  
Elen De Souza Tolentino ◽  
Eduardo Dias-Ribeiro ◽  
Marina de Lourdes Calvo Fracasso ◽  
Alfredo Franco Queiroz ◽  
...  

Tooth avulsion is a complex injury that affects the pulp tissue, periodontal ligament and alveolar bone. It is more frequent in children aged 7 to 11 years. The prognosis is directly related to the period during which the tooth is outside the socket; there is consensus in the literature that the shorter this period, the higher will be the possibility of pulp revascularization and reattachment of periodontal ligament fibers. The need of maintenance of the avulsed tooth in an adequate medium is also known. This study reports a case of complex replantation after avulsion, in which the care was provided 48 hours after the trauma and the tooth was kept dry by the patient, thus suggesting a treatment option for these cases. The avulsed tooth was cleaned and submitted to endodontic treatment; a rigid retainer was used for 7 days and the calcium hydroxide dressing was constantly replaced for 12 months. After 28 months, the tooth exhibited clinical aspect of normality and the radiographic examination revealed a slight alteration at the apical portion of the root. It was concluded that this treatment planning may be a good option in cases of tooth avulsion with late replantation; even though the conditions of care were unfavorable and contraindicated by the scientific literature and the prognosis was impaired, a considerable benefit was achieved for the patient, since the treatment allowed its immediate reintegration to the social relationships, as well as maintenance of facial growth and development.


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