Translation Approach for Dentine Regeneration Using GSK-3 Antagonists

Journal of Dental Research
L K ZauggPaul T Sharpe

Abstract

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 o...Continue Reading

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Citations

Jun 10, 2020·International Journal of Molecular Sciences·Juliana BaranovaEdda Tobiasch
Sep 6, 2020·International Journal of Molecular Sciences·Anahid A BirjandiPaul T Sharpe
Dec 3, 2020·Odontology·Matthias Widbiller, Gottfried Schmalz
Nov 23, 2020·International Journal of Paediatric Dentistry·Janita ShahSadna Rajan
Aug 25, 2020·Injury·Marianne Comeau-GauthierGeraldine Merle
Jan 19, 2021·Stem Cell Reviews and Reports·Cheng LiangWeidong Tian
Nov 21, 2020·Scientific Reports·Vitor C M NevesPaul T Sharpe
Jun 22, 2021·Journal of Dental Research·A AlaohaliP T Sharpe
Jul 3, 2021·International Journal of Molecular Sciences·Sarah Hani ShoushrahEdda Tobiasch
Aug 18, 2021·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Yüksel KorkmazJames Deschner
Aug 27, 2021·ACS Biomaterials Science & Engineering·Wen QinLi-Na Niu

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Methods Mentioned

BETA
Reverse Transcription Polymerase
PCA

Software Mentioned

GraphPad
GraphPad Prism
Microview
MATLAB

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