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-Nakamura, 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 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-Nakamura and Norihisa Uehara and Kazuaki Nonaka and Toshio Kukita and Takayoshi Yamaza",
year = "2019",
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language = "English",
volume = "45",
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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-Nakamura, Yukari

AU - Uehara, Norihisa

AU - Nonaka, Kazuaki

AU - Kukita, Toshio

AU - Yamaza, Takayoshi

PY - 2019/5

Y1 - 2019/5

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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JO - Journal of Endodontics

JF - Journal of Endodontics

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