The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome.
The calcium dynamics of human dental pulp stem cells stimulated with tricalcium silicate-based cements determine their differentiation and mineralization outcome.
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DOI：
10.1038/s41598-020-80096-5
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发表时间：
2021-01-12
影响因子：
4.6
通讯作者：
Leybaert L
中科院分区：
文献类型：
--
作者：
Rathinam E;Govindarajan S;Rajasekharan S;Declercq H;Elewaut D;De Coster P;Martens L;Leybaert L
钙（Ca2+）信号在牙髓和牙本质再生中起着不可或缺的作用，但基于硅酸三钙（tcs）的牙科生物材料刺激人牙髓干细胞（hDPSCs）的Ca2+反应仍未得到充分研究。本研究的目的是鉴定和关联细胞外Ca2+浓度，细胞内Ca2+动力学，pH值，细胞毒性，基因表达和矿化能力的人牙髓干细胞（hDPSCs）刺激两种不同的tcs为基础的生物材料：Biodentine和prooroot白色MTA。将hdpsc暴露于生物材料中，与覆盖介质接触，随后测量细胞外Ca2+和pH值，以及细胞内Ca2+变化。然后评估信使RNA表达（BGLAP, TGF-β， MMP1和BMP2），细胞毒性（MTT和TUNEL）和矿化电位（茜素红和Von Kossa染色）。Biodentine在α-MEM培养基中释放的Ca2+明显多于prooroot WMTA，但这对hdpsc没有细胞毒性影响。与prooroot WMTA相比，biodentine连接的Ca2+释放量较大，导致细胞内Ca2+动力学发生改变，其最大振幅更高，上升时间更快，Ca2+变化曲线下面积增加。细胞内Ca2+螯合实验表明，生物材料触发的Ca2+动力学影响干细胞相关基因表达、细胞分化和矿化电位。综上所述，hdpsc中生物材料特异性Ca2+动力学决定了分化和矿化结果，Ca2+动力学的增加增强了矿化。
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.
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影响因子：
3
作者：
Jung S;Mielert J;Kleinheinz J;Dammaschke T
通讯作者：
Dammaschke T
影响因子：
4
作者：
Forostyak, Oksana;Romanyuk, Nataliya;Dayanithi, Govindan
通讯作者：
Dayanithi, Govindan
影响因子：
4.2
作者：
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通讯作者：
Bhat, Kadengodlu Seetharama
影响因子：
5
作者：
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通讯作者：
Camilleri, J.
影响因子：
--
作者：
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通讯作者：
Pozos-Guillen, Amaury