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Investigation for pathogenesis of jaw deformity focusing on epigenetics: application to new therapeutic strategies

Research Project

Project/Area Number 20K10120
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionKyushu University

Principal Investigator

YAMADA Tomohiro  九州大学, 歯学研究院, 共同研究員 (60335619)

Co-Investigator(Kenkyū-buntansha) 森 悦秀  九州大学, 歯学研究院, 教授 (00231639)
杉山 悟郎  九州大学, 歯学研究院, 助教 (00722828)
山本 健  久留米大学, 医学部, 教授 (60274528)
高橋 一郎  九州大学, 歯学研究院, 教授 (70241643)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords顎変形症 / 下顎骨 / 咀嚼筋 / エピジェネティクス / メチル化
Outline of Research at the Start

本研究では筋の特性に影響を与える因子として、環境・遺伝子相互作用に関連するエピジェネティックな制御機構に着目し、顎骨の変形に筋関連遺伝子のサイレンシングが関与しているかを調べる。エピジェネティックな制御機構にはDNAメチル化、ヒストンアセチル化/メチル化によるものが知られており、本研究では咬筋生検材料を用いて咬筋のマクロ的所見、筋線維のタイプに加え、網羅的メチル化解析を含め関連遺伝子の発現抑制と顎変形のパターンとを比較検討する。

Outline of Final Research Achievements

When the thickness and cross-sectional area of the masseter muscle were analyzed from CT images of 27 patients with mandibular prognathism with mandibular asymmetry and 11 patients as a control group, there was no difference in the thickness and cross-sectional area of the masseter muscle in the patient group from left to right, but the patient group had a thinner thickness than the control group. Therefore, it was considered that skeletal classification such as mandibular protrusion contributed more to the morphological volume of the muscles than the left-right difference.
From FY2022 to FY2023, methylation of masseter muscle DNA was examined in 18 patients and 5 controls. As a result, approximately 150% more methylated DNA was detected in the patient group than in the control group. This suggests that epigenetic control mechanisms are involved in the pathogenesis of jaw deformities.

Academic Significance and Societal Importance of the Research Achievements

われわれは咀嚼筋の機能異常に起因する下顎骨の変形が多くの顎変形症の主因 となっている症例が多いとの仮説をたてた。筋の性状を決定する要因としては、遺伝的素因と環境的素因が考えられる。そこで本研究では 環境・遺伝子相互作用に関連するエピジェネティックな制御機構に着目した。本研究の結果、顎変形症患者の咬筋特性に対するエピジェネティックな制御機構が明らかになれば、筋のエクササイズなどの機能訓練、速筋化を促進するクレンブテロールや脱メチル化剤などの薬物療法、脱メチル化作用をもつ食品などによる食事療法など、保存的治療法や予防的先制医療に応用できる可能性が期待できる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2022

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Three-Dimensional Geometric Morphometry of Facial Soft Tissue Changes After Bilateral Sagittal Split Ramus Osteotomy.2022

    • Author(s)
      Al Bougha S, Nakano H, Yasuda K, Suzuki K, Yamada T, Takahashi I, Ueno T, Mori Y.
    • Journal Title

      J Craniofac Surg.

      Volume: 34

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Presurgical simulation in oral and maxillofacial surgery, risk management and prediction of appearance.2022

    • Author(s)
      Yamada T, Anantanarayanan P, Mori Y
    • Organizer
      14th World Congress of The Cleft Lip and Palate Foundation
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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