title: Mineral trioxide aggregate induces osteoblastogenesis via Atf6.
abstract: 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 inducedBglap(osteocalcin) but notBmp2(bone morphogenetic protein-2) mRNA expression. We observed induction ofAtf6(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 enhancedBglapmRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to theBglappromoter 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.
authors.affiliation: Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Toyonobu
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuzawa
authors.affiliation: Department of General Clinical Medicine, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Division of Endodontics, Department of Conservative Dentistry, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kato
keywords: Atf6; Bone regeneration; Endodontics; Mineral trioxide aggregate; Osteoblastgenesis