Histol Histopathol, Vol 34, Tatullo et al. (original) (raw)

Review

Small molecule GSK-3 antagonists play a pivotal role in reducing the local inflammatory response, in promoting resident stem cell activation and in improving tissue repairing in regenerative dentistry

Marco Tatullo1,2, Irina Makeeva2, Sandro Rengo3, Carlo Rengo3, Gianrico Spagnuolo2,3 and Bruna Codispoti1

1Tecnologica Research Institute, Stem Cells Unit, Crotone, Italy, 2Department of Therapeutic Dentistry, "Sechenov" University of Moscow, Moscow, Russia and 3Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", Naples, Italy

Offprint requests to: Prof. Marco Tatullo, Scientific Director - Tecnologica Research Institute, St. E. Fermi - Crotone, Italy, Professor - IM Sechenov First Moscow State Medical University, Moscow, Russia. e-mail: marco.tatullo@tecnologicasrl.com

Summary. Regenerative dentistry is attracting growing interest in the scientific community, mainly because of its translational and promising therapeutic approach. The latest research carried out by the scientific community are aimed at triggering the local cellular response, in order to induce a physiological self-repairing of damaged oral tissues. Such physiological processes mainly involve the activation of local stem cell populations: mesenchymal stem cells, in fact, retain the ability to proliferate and to differentiate towards functional mature elements, thus leading towards healing of damaged tissues. Glycogen Synthase Kinase-3 (GSK-3) is a key-regulator of the Wnt/β-catenin pathway; it phosphorylates β-catenin, that then is degraded in the cytosol. The activation of such signalling, mediated by Wnt ligand/receptor association, inhibits GSK-3, leading to translocation of β-catenin to the nucleus and to gene transcription. Selective inhibitors of GSK-3 have been linked to the activity of Wnt signalling and to the regeneration of injured tissues, including complex dental and oral structures. Small Molecule GSK-3 Antagonists are the most interesting class of molecules acting with a "Bystander effect": reducing local inflammation and local bone resorption and triggering the activity and differentiation of resident "sleeping" MSCs. The aim of this narrative topical review is to describe the current knowledge on the role of small molecule GSK-3 antagonists in regenerative dentistry, with strategic insights towards the translational applications in nanomaterials in dentistry and in dental repairing. Histol Histopathol 34, 1195-1203 (2019)

Key words: GSK-3 inhibitors, Tissue engineering, Dental regeneration, Nano-carriers, Small molecules

DOI: 10.14670/HH-18-133