Dental stem cell signaling pathway activation in response to hydraulic calcium silicate-based endodontic cements: A systematic review of in vitro studies

Abstract

Objective: To present a qualitative synthesis of in vitro studies which analyzed human dental stem cell (DSC) molecular signaling pathway activation in response to hydraulic calcium silicate-based cements (HCSCs).

Methods: A systematic electronic search was performed in Medline, Scopus, Embase, Web of Science and SciELO databases on January 20 and last updated on March 20, 2020. In vitro studies assessing the implication of signaling pathways in activity related marker (gene/protein) expression and mineralization induced by HCSCs in contact with human DSCs were included.

Results: The search identified 277 preliminary results. After discarding duplicates, and screening of titles, abstracts, and full texts, 13 articles were considered eligible. All of the materials assessed by the included studies showed positive results in cytocompatibility and/or bioactivity assays. ProRoot MTA and Biodentine were the modal HCSCs studied, hDPSCs were the modal cell variant used, and the most studied signaling pathway was MAPK. In vitro assays measuring the expression of activity-related markers and mineralized nodule formation evidenced the involvement of MAPK (and its subfamilies ERK, JNK and P38), NF-κB, Wnt/β-catenin, BMP/Smad and CAMKII pathways in the biological response of DSCs to HCSCs.

Significance: HCSCs considered in the present review elicited a favorable biological response from a variety of DSCs in vitro, thus supporting their use in biologically-based endodontic procedures. MAPK, NF-κβ, Wnt/β-catenin, BMP/Smad and CAMKII signaling pathways have been proposed as potential mediators in the biological interaction between DSCs and HCSCs. Understanding the signaling processes involved in tissue repair could lead to the development of new biomaterial compositions targeted at enhancing these mechanisms through biologically-based procedures.

Keywords: Bioactivity; Biomineralization; Calcium silicate-based cements; Dental stem cells; In vitro; Signaling pathways.