Department of Oral Medicine, School of Dentistry, Kyungpook National University, Daegu, Korea.
Department of Biochemistry, School of Dentistry, Institute for Hard Tissue and Bone Regeneration, Kyungpook National University, Daegu, Korea.
J Endod. 2017 Dec;43(12):2041-2047. doi: 10.1016/j.joen.2017.07.018. Epub 2017 Oct 9.
The aim of this study was to evaluate in vitro and ex vivo roles of bortezomib, a proteasome inhibitor that binds to the active site of the 26S proteasome, in tertiary dentin formation.
We established pulpal access cavity preparation that was treated with or without bortezomib before direct pulp capping with a calcium hydroxide-based material. We also analyzed bone morphogenetic protein (Bmp)- and Wnt-related signaling molecules using quantitative real-time polymerase chain reaction.
In the short-term observation period, the bortezomib-treated pulp specimens showed the period-altered immunolocalization patterns of nestin, CD31, and myeloperoxidase, whereas the control specimens did not. The bortezomib-treated group showed a complete dentin bridge with very few irregular tubules after 42 days. The micro-computed tomographic images showed more apparent dentin bridge structures in the treated specimens than were in the controls. Quantitative real-time polymerase chain reaction analysis showed up-regulated Bmp and Wnt.
These findings revealed that treatment with 1 μmol/L bortezomib induced reparative dentin formation that facilitated the maintenance of the integrity of the remaining pulpal tissue via early vascularization and regulation of Bmp and Wnt signaling.
本研究旨在评估蛋白酶体抑制剂硼替佐米在三进制牙本质形成中的体外和体内作用,该抑制剂与 26S 蛋白酶体的活性部位结合。
我们建立了牙髓腔暴露模型,在直接盖髓前用或不用硼替佐米处理,并用钙基氢氧化材料覆盖。我们还使用实时定量聚合酶链反应分析了骨形态发生蛋白(BMP)和 Wnt 相关信号分子。
在短期观察期内,硼替佐米处理的牙髓标本显示巢蛋白、CD31 和髓过氧化物酶的免疫组织化学定位模式发生了改变,而对照标本则没有。硼替佐米处理组在 42 天后形成了完整的牙本质桥,仅有少量不规则的小管。微计算机断层扫描图像显示处理组的牙本质桥结构比对照组更明显。实时定量聚合酶链反应分析显示 Bmp 和 Wnt 表达上调。
这些发现表明,用 1μmol/L 的硼替佐米处理可诱导修复性牙本质形成,通过早期血管化和调节 BMP 和 Wnt 信号来维持剩余牙髓组织的完整性。