九州大学 研究者情報
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御手洗 裕美(みたらいひろみ) データ更新日:2024.06.03

助教 /  九州大学病院 口腔包括診療科 口腔総合診療科


主な研究テーマ
歯根膜幹細胞誘導因子の同定と新規歯周組織再生療法の開発
キーワード:歯根膜、幹細胞、エクソソーム
2018.06.
Transgelinが歯根膜細胞の恒常性維持に及ぼす影響
キーワード:ヒト歯根膜細胞
2013.04~2017.03.
従事しているプロジェクト研究
歯小嚢に発現するlncRNAを介したIGFシグナル応用新規歯周組織再生療法の樹立
2022.04~2025.03, 代表者:御手洗裕美, 九州大学病院.
アンキローシス発生機序探索の鍵となる新規TGF-βシグナル関連因子分子機構の解明
2019.04~2022.03.
歯根膜幹細胞誘導因子の同定と新規歯周組織再生療法の開発
2018.06~2018.06.
研究業績
主要原著論文
1. 信太実有, 御手洗裕美, 和田尚久, 患者情報やコミュニケーション技法を積極的に活用し歯科治療が可能となった 1 症例, 2022.12.
2. NaatiFakatava, HiromiMitarai, AsukaYuda, AkiraHaraguchi, HirokoWada, DaigakuHasegawa, HidefumiMaeda, NaohisaWada, Actin alpha 2, smooth muscle, a transforming growth factor-β1-induced factor, regulates collagen production in human periodontal ligament cells via Smad2/3 pathway, J Dent Sci, 2023.04, Background/purpose: Actin alpha 2, smooth muscle (ACTA2) is an actin isoform that forms the cytoskeleton. Actin plays a crucial role in numerous cellular functions. ACTA2 is a marker of functional periodontal ligament (PDL) fibroblasts and is upregulated by transforming growth factor-β1 (TGF-β1); however, the underlying function of ACTA2 in PDL tissue is unknown. We aimed to examine the localization and potential function of ACTA2 in PDL tissues and cells.

Materials and methods: RNA expression was determined using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and quantitative RT-PCR. Protein expression was determined using immunofluorescence staining and Western blot analysis. Soluble and insoluble collagen production was examined using the Sircol collagen assay and picrosirius red staining, respectively. Small interfering RNA (siRNA) was used for knockdown assay to examine the effect of ACTA2 in human PDL cells.

Results: ACTA2 expression was observed in human primary PDL cells and PDL cell line (2-23 cells). TGF-β1 upregulated ACTA2, collagen type Ⅰ alpha1 chain (COL1A1), periostin (POSTN), and fibrillin-Ⅰ(FBN1) expression and soluble and insoluble collagen production in 2-23 cells. However, ACTA2 depletion by siRNA strongly suppressed PDL-related gene expression and collagen production compared with those of TGF-β1-stimulated control cells. Furthermore, ACTA2 knockdown significantly suppressed the phosphorylation of Smad2 and Smad3.

Conclusion: ACTA2 plays a crucial role in PDL-related marker expression and collagen production via Smad2/3 phosphorylation. Our findings might contribute to the development of novel and effective periodontal therapies..
3. Hiromi Mitarai, Naohisa Wada, Daigaku Hasegawa, Shinichiro Yoshida, Mai Arima, Atsushi Tomokiyo, Sayuri Hamano, Suguru Serita, Hiroyuki Mizumachi, Hidefumi Maeda, Transgelin mediates transforming growth factor-β1-induced proliferation of human periodontal ligament cells., Journal of periodontal research., 10.1111/jre.12466, 52, 6, 984-993, 2017.12, BACKGROUND AND OBJECTIVE:
Human periodontal ligament cells (HPDLCs) express transforming growth factor-β1 (TGF-β1) that regulates differentiation and proliferation, and plays key roles in homeostasis of PDL tissue. Transgelin is a cytoskeleton-associated protein with an Smad-binding element in its gene promoter region. In this study, we examined the localization and potential function of transgelin in PDL tissue and cells.

MATERIAL AND METHODS:
Microarray analysis of HPDLC lines (2-14, 2-23 and 2-52) was performed. Expression of transgelin in HPDLCs was examined by quantitative reverse transcription-polymerase chain reaction, immunofluorescence staining and western blot analysis. Effects of TGF-β1 and its signaling inhibitor, SB431542, on transgelin expression in HPDLCs were examined by western blot analysis. The effects of transgelin knockdown by small interfering RNA (siRNA) on HPDLC proliferation stimulated by TGF-β1 were assessed by WST-1 assay.

RESULTS:
In microarray and quantitative reverse transcription-polymerase chain reaction analyses, the expression levels of transgelin (TAGLN) in 2-14 and 2-23 cells, which highly expressed PDL markers such as periostin (POSTN), tissue non-specific alkaline phosphatase (ALPL), α-smooth muscle actin (ACTA2) and type I collagen A1 (COL1A1), was significantly higher than those in 2-52 cells that expressed PDL markers weakly. Immunohistochemical and immunofluorescence staining revealed expression of transgelin in rat PDL tissue and HPDLCs. In HPDLCs, TGF-β1 treatment upregulated transgelin expression, whereas inhibition of the type 1 TGF-β1 receptor by SB431542 suppressed this upregulation. Furthermore, TAGLN siRNA transfection did not promote the proliferation of HPDLCs treated with TGF-β1. The expression levels of CCNA2 and CCNE1, which regulate DNA synthesis and mitosis through the cell cycle, were also not upregulated in HPDLCs transfected with TAGLN siRNA.

CONCLUSION:
Transgelin is expressed in PDL tissue and might have a role in HPDLC proliferation induced by TGF-β1 stimulation..
主要学会発表等
1. 御手洗裕美、Naati Fakatava、王恕心、冉子晴、祐田明香、原口晃、孫偉浩、和田尚久, スーパーMTAペーストはヒト前骨芽細胞の石灰化誘導能を促進する, 日本歯科保存学会2023年度春季大会 (第158回), 2023.06.
2. 御手洗 裕美, 術前の口腔内診査と診断の重要性を学んだ2つの症例, 第15回日本総合歯科学会学術大会, 2022.11.
3. Fakatava Naati、御手洗裕美、祐田明香、長谷川大学、前田英史、和田尚久, The Role of Acta2 in Periodontal Ligament cell stimulated with TGF-β1, 日本歯科保存学会, 2020.06.
4. 御手洗裕美、祐田明香、Fakatava Naati、長谷川大学、前田英史、和田尚久, Transgelinは、Integrinを介した細胞外基質への接着に関与する, 日本歯科保存学会, 2020.06.
学会活動
所属学会名
International Association for Dental Research
大阪大学歯学会
日本歯内療法学会
日本顕微鏡歯科学会
日本歯科保存学会
学会大会・会議・シンポジウム等における役割
2021.04.24~2021.04.25, 顕微鏡歯科学会, 実行委員.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2022年度~2025年度, 若手研究, 代表, 歯小嚢に発現するlncRNAを介したIGFシグナル応用新規歯周組織再生療法の樹立.
2019年度~2021年度, 若手研究, 代表, アンキローシス発生機序探索の鍵となる新規TGF-βシグナル関連因子分子機構の解明.
2017年度~2018年度, 若手研究(スタートアップ), 代表, 歯根膜幹細胞誘導因子の同定と新規歯周組織再生療法の開発.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。