The elucidation of the onset mechanism of periodontitis focusing on amelotin in junctional epithelium

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21385
• Project/Area Number (Other): 18H06297 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0907:Oral science and related fields
• Research Institution: Nihon University
• Principal Investigator: TAKAI Mizuho (山崎瑞穂) 日本大学, 松戸歯学部, 専修医 (20822620)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: アメロチン / microRNA / TNF-α / 遺伝子転写調節 / 歯肉上皮細胞 / 接合上皮

Outline of Final Research Achievements

MicroRNA is a small non-coding RNA that regulates gene expression at the post-transcriptional level by binding to the 3’-untranslated region (3’-UTR) of target mRNAs. Amelotin (AMTN) is an enamel protein that is localized in the internal basal lamina of junctional epithelium (JE). In this study, we have analyzed the effect of miR-200b on the AMTN gene transcription induced by TNF-α in human gingival epithelial cells (Ca9-22). TNF-α-induced AMTN mRNA levels were partially inhibited by miR-200b overexpression. TNF-α-induced IKKβ mRNA and protein levels were almost completely inhibited by miR-200b. These results suggest that miR-200b supresses AMTN gene expression directly or indirectly by targeting to AMTN and IKKβ mRNAs in the human gingival epithelial cells.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

歯肉接合上皮に特異的に発現するタンパク質であるアメロチンは、上皮性付着への関与が示唆され、TNF-α刺激で発現が増加する。本研究では、ヒト歯肉上皮細胞におけるTNF-α誘導性のアメロチン遺伝子発現は、miR-200b過剰発現により直接的に抑制され、さらにIKKβを標的として間接的に抑制される可能性が示された。このことから、歯周病発症に重要な領域である接合上皮におけるアメロチン遺伝子調節機構の、炎症環境下での複雑な動態の一部が明らかとなった。本研究の成果は、歯周病発症メカニズムを解き明かす重要な足掛かりとなると考えられる。