Mineral trioxide aggregate induces osteoblastogenesis via Atf6

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...

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Main Authors: Toyonobu Maeda, Atsuko Suzuki, Satoshi Yuzawa, Yuh Baba, Yuichi Kimura, Yasumasa Kato
Format: Article
Language:English
Published: Elsevier 2015-06-01
Series:Bone Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352187215000078
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author Toyonobu Maeda
Atsuko Suzuki
Satoshi Yuzawa
Yuh Baba
Yuichi Kimura
Yasumasa Kato
author_facet Toyonobu Maeda
Atsuko Suzuki
Satoshi Yuzawa
Yuh Baba
Yuichi Kimura
Yasumasa Kato
author_sort Toyonobu Maeda
collection DOAJ
description 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.
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spelling doaj.art-317aa60129974a34943d2c1b675064882022-12-22T03:51:24ZengElsevierBone Reports2352-18722015-06-012C364310.1016/j.bonr.2015.03.003Mineral trioxide aggregate induces osteoblastogenesis via Atf6Toyonobu Maeda0Atsuko Suzuki1Satoshi Yuzawa2Yuh Baba3Yuichi Kimura4Yasumasa Kato5Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, JapanDepartment of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, JapanDepartment of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, JapanDepartment of General Clinical Medicine, Ohu University School of Dentistry, Koriyama 963-8611, JapanDivision of Endodontics, Department of Conservative Dentistry, Ohu University School of Dentistry, Koriyama 963-8611, JapanDepartment of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama 963-8611, JapanMineral 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.http://www.sciencedirect.com/science/article/pii/S2352187215000078OsteoblastgenesisEndodonticsBone regenerationMineral trioxide aggregateAtf6
spellingShingle Toyonobu Maeda
Atsuko Suzuki
Satoshi Yuzawa
Yuh Baba
Yuichi Kimura
Yasumasa Kato
Mineral trioxide aggregate induces osteoblastogenesis via Atf6
Bone Reports
Osteoblastgenesis
Endodontics
Bone regeneration
Mineral trioxide aggregate
Atf6
title Mineral trioxide aggregate induces osteoblastogenesis via Atf6
title_full Mineral trioxide aggregate induces osteoblastogenesis via Atf6
title_fullStr Mineral trioxide aggregate induces osteoblastogenesis via Atf6
title_full_unstemmed Mineral trioxide aggregate induces osteoblastogenesis via Atf6
title_short Mineral trioxide aggregate induces osteoblastogenesis via Atf6
title_sort mineral trioxide aggregate induces osteoblastogenesis via atf6
topic Osteoblastgenesis
Endodontics
Bone regeneration
Mineral trioxide aggregate
Atf6
url http://www.sciencedirect.com/science/article/pii/S2352187215000078
work_keys_str_mv AT toyonobumaeda mineraltrioxideaggregateinducesosteoblastogenesisviaatf6
AT atsukosuzuki mineraltrioxideaggregateinducesosteoblastogenesisviaatf6
AT satoshiyuzawa mineraltrioxideaggregateinducesosteoblastogenesisviaatf6
AT yuhbaba mineraltrioxideaggregateinducesosteoblastogenesisviaatf6
AT yuichikimura mineraltrioxideaggregateinducesosteoblastogenesisviaatf6
AT yasumasakato mineraltrioxideaggregateinducesosteoblastogenesisviaatf6