Mineral trioxide aggregate induces osteoblastogenesis via Atf6.
Mineral trioxide aggregate induces osteoblastogenesis via Atf6.
复制标题
DOI：
10.1016/j.bonr.2015.03.003
复制
发表时间：
2015-06
期刊：
影响因子：
2.5
通讯作者：
Kato Y
中科院分区：
文献类型：
--
作者：
Maeda T;Suzuki A;Yuzawa S;Baba Y;Kimura Y;Kato Y
矿物三氧化物聚集体（MTA）已被推荐用于牙髓病的各种用途。为了了解MTA对牙槽骨的影响，我们使用MC 3 T3-E1细胞检测MTA是否诱导成骨细胞分化。MTA以剂量和时间依赖性的方式增强矿化伴随着碱性磷酸酶活性。MTA增加胶原（I型和III型）和基质金属蛋白酶（MMP-9和MMP-13）的产生，表明MTA影响骨基质重塑。MTA也诱导Bglap（骨钙素），但不Bmp 2（骨形态发生蛋白-2）mRNA的表达。我们观察到诱导Atf 6（激活转录因子6，内质网（ER）应激反应转录因子）mRNA的表达和激活的Atf 6 MTA治疗。p50 Atf 6（Atf 6的活性形式）的强制表达显著增强Bglap mRNA表达。染色质免疫沉淀试验用于研究MTA处理后p50 Atf 6与Bglap启动子区域结合的增加。此外，通过引入Tet-on Atf 6 shRNA表达载体敲低Atf 6基因表达，废除了MTA诱导的矿化。这些结果表明，MTA诱导体外成骨细胞通过Atf 6-骨钙素轴作为ER应激信号。因此，MTA在根管治疗中可能会影响牙髓感染引起的牙槽骨吸收区的愈合。
Mineral trioxide aggregate (MTA) has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III) and matrix metalloproteinases (MMP-9 and MMP-13), suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin) but not Bmp2 (bone morphogenetic protein-2) mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER) stress response transcription factor) mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6) markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.