Department of Physiology, School of Dentistry, Seoul National University and Dental Research Institute, Seoul, South Korea.
Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, South Korea.
Biomaterials. 2017 May;127:107-116. doi: 10.1016/j.biomaterials.2017.02.038. Epub 2017 Feb 28.
Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs). We found that MTA activates diverse CaSR downstream pathways; notably, CaSR activation essentially requires dual modulation of extracellular Ca and pH via MTA. Among the CaSR downstream pathways, Ca mobilization from intracellular stores by the phospholipase C pathway plays an important role in osteogenic differentiation of hDPCs by regulating transcriptional activity. Our findings shed light on the signal transduction mechanism of MTA, thus providing a crucial molecular basis for the use of MTA in regenerative dental therapy.
矿物三氧化物聚合体（MTA）是一种基于硅酸钙的生物活性材料，已广泛应用于牙科领域。MTA 具有多种生物学功能和优异的临床效果，备受关注。然而，目前对于解释 MTA 生物学活性的细胞内信号通路的了解还很有限。在这里，我们首次通过对人牙髓细胞（hDPC）的多种活体成像技术，阐明了细胞外钙敏感受体（CaSR）是 MTA 诱导的生物学反应的主要信号介质。我们发现 MTA 激活了多种 CaSR 下游通路；值得注意的是，CaSR 的激活本质上需要通过 MTA 双重调节细胞外 Ca 和 pH。在 CaSR 下游通路中，通过磷脂酶 C 通路从细胞内储存中释放 Ca 对于 hDPC 的成骨分化起着重要作用，通过调节转录活性来实现。我们的研究结果揭示了 MTA 的信号转导机制，从而为 MTA 在再生牙科治疗中的应用提供了重要的分子基础。
