标题：The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome
摘要：Calcium (Ca2 ) signalling plays an indispensable role in dental pulp and dentin regeneration, but the Ca2 responses of human dental pulp stem cells (hDPSCs) stimulated with tricalcium silicate-based (TCS-based) dental biomaterials remains largely unexplored. The objective of the present study was to identify and correlate extracellular Ca2 concentration, intracellular Ca2 dynamics, pH, cytotoxicity, gene expression and mineralization ability of human dental pulp stem cells (hDPSCs) stimulated with two different TCS-based biomaterials: Biodentine and ProRoot white MTA. The hDPSCs were exposed to the biomaterials, brought in contact with the overlaying medium, with subsequent measurements of extracellular Ca2 and pH, and intracellular Ca2 changes. Messenger RNA expression (BGLAP, TGF-β, MMP1 and BMP2), cytotoxicity (MTT and TUNEL) and mineralization potential (Alizarin red and Von Kossa staining) were then evaluated. Biodentine released significantly more Ca2 in the α-MEM medium than ProRoot WMTA but this had no cytotoxic impact on hDPSCs. The larger Biodentine-linked Ca2 release resulted in altered intracellular Ca2 dynamics, which attained a higher maximum amplitude, faster rise time and increased area under the curve of the Ca2 changes compared to ProRoot WMTA. Experiments with intracellular Ca2 chelation, demonstrated that the biomaterial-triggered Ca2 dynamics affected stem cell-related gene expression, cellular differentiation and mineralization potential. In conclusion, biomaterial-specific Ca2 dynamics in hDPSCs determine differentiation and mineralization outcomes, with increased Ca2 dynamics enhancing mineralization.
