Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla

Yosuke Tanaka, Soichiro Sonoda, Haruyoshi Yamaza, Sara Murata, Kento Nishida, Yukari Kyumoto, Norihisa Uehara, Kazuaki Nonaka, Toshio Kukita, Takayoshi Yamaza

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Abstract

Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs])are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA)on odontogenic differentiation of SCAPs in vitro and in vivo. Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. Results: ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. Conclusions: These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration.

Original languageEnglish
Pages (from-to)591-598.e6
JournalJournal of Endodontics
Volume45
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Aspirin
Stem Cells
Tooth Root
NFI Transcription Factors
Small Interfering RNA
Regeneration
1-Phosphatidylinositol 4-Kinase
Dentin
Phosphatidylinositols
Tooth
Proteins
Up-Regulation
Down-Regulation
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

Cite this

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title = "Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla",
abstract = "Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs])are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA)on odontogenic differentiation of SCAPs in vitro and in vivo. Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. Results: ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. Conclusions: These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration.",
author = "Yosuke Tanaka and Soichiro Sonoda and Haruyoshi Yamaza and Sara Murata and Kento Nishida and Yukari Kyumoto and Norihisa Uehara and Kazuaki Nonaka and Toshio Kukita and Takayoshi Yamaza",
year = "2019",
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language = "English",
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TY - JOUR

T1 - Acetylsalicylic Acid Treatment and Suppressive Regulation of AKT Accelerate Odontogenic Differentiation of Stem Cells from the Apical Papilla

AU - Tanaka, Yosuke

AU - Sonoda, Soichiro

AU - Yamaza, Haruyoshi

AU - Murata, Sara

AU - Nishida, Kento

AU - Kyumoto, Yukari

AU - Uehara, Norihisa

AU - Nonaka, Kazuaki

AU - Kukita, Toshio

AU - Yamaza, Takayoshi

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs])are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA)on odontogenic differentiation of SCAPs in vitro and in vivo. Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. Results: ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. Conclusions: These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration.

AB - Introduction: Stem cells isolated from the root apical papilla of human teeth (stem cells from the apical papilla [SCAPs])are capable of forming tooth root dentin and are a feasible source for bioengineered tooth root regeneration. In this study, we examined the effect of acetylsalicylic acid (ASA)on odontogenic differentiation of SCAPs in vitro and in vivo. Methods: SCAPs were cultured under odontogenic conditions supplemented with or without ASA. ASA-treated SCAPs were also subcutaneously transplanted into immunocompromised mice. Results: ASA accelerates in vitro and in vivo odontogenic differentiation of SCAPs associated with down-regulation of runt-related nuclear factor 2 and up-regulation of specificity protein 7, nuclear factor I C, and dentin phosphoprotein. ASA up-regulated the phosphorylation of AKT in the odontogenic SCAPs. Of interest, pretreatments with phosphoinositide 3-kinase inhibitor LY294402 and small interfering RNA for AKT promoted ASA-induced in vitro and in vivo odontogenic differentiation of SCAPs. LY294402 and small interfering RNA for AKT also suppressed the ASA-induced expression of runt-related nuclear factor 2 and enhanced ASA-induced expression of specificity protein 7, nuclear factor I C, and dentin phosphoprotein in SCAPs. Conclusions: These findings suggest that a combination of ASA treatment and suppressive regulation of the phosphoinositide 3-kinase–AKT signaling pathway is a novel approach for SCAP-based tooth root regeneration.

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U2 - 10.1016/j.joen.2019.01.016

DO - 10.1016/j.joen.2019.01.016

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SP - 591-598.e6

JO - Journal of Endodontics

JF - Journal of Endodontics

SN - 0099-2399

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