A New Calcium Silicate–based Bioceramic Material Promotes Human Osteo- and Odontogenic Stem Cell Proliferation and Survival via the Extracellular Signal-regulated Kinase Signaling Pathway

Abstract Introduction The purpose of this study was to investigate odontogenic and osteogenic cell adhesion, proliferation, and survival on the surface of a newly developed bioceramic material (EndoSequence Root Repair Material [RRM]; Brasseler USA, Savannah, GA) and compare it with mineral trioxide aggregate (gray MTA) (ProRoot MTA; Dentsply Tulsa Dental, Tulsa, OK). A potential role of extracellular signal-regulated kinase (ERK) signaling in the RRM/MTA-induced cellular activities was also investigated. Methods Human bone marrow mesenchymal stem cells, periodontal ligament stem cells, and dental pulp stem cells were cultured on RRM- or MTA-coated slides. Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays after 1, 3, and 5 days of growth. Cell survival was assessed under serum starvation (0.5% and 0.2% serum) using MTT assays. RRM and MTA surface characteristics and cell morphology were studied using a scanning electron microscope. The role of ERK signaling in RRM/MTA-induced cell proliferation/survival was studied using an ERK-specific inhibitor. Results All cell types firmly attached to RRM- and MTA-coated plates. The coated surfaces had a granular appearance under the scanning electron microscope. Compared with those grown on uncoated plates, the cells on MTA/RRM-coated plates appeared healthy and smaller. Cell proliferation was significantly higher on RRM/MTA-coated surfaces (2- to 3-fold in cell number). The mitogenic effect on periodontal ligament stem cells and dental pulp stem cells was more pronounced with RRM than MTA (49% and 26% higher, respectively), but human bone marrow mesenchymal stem cells responded to both materials similarly. In serum-deprived conditions, significantly more cells (2- to 3-fold) survived on RRM/MTA surfaces. The cells grown on RRM/MTA surfaces showed sustained up-regulation of ERK phosphorylation, and blocking ERK signaling with U0126 significantly reduced RRM- and MTA-dependent cell survival. Conclusions MTA and RRM are biocompatible and promote cell proliferation and survival in an ERK-dependent manner.