Oxidative stress as an onset mechanism for cleft lip and palate and a possible target for the development of preventive methods

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11807
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Kyushu University
• Principal Investigator: Kato Hiroki 九州大学, 歯学研究院, 助教 (30452709)
• Co-Investigator(Kenkyū-buntansha): 佐藤 浩 九州大学, 歯学研究院, 助教 (00421313) ; 廣藤 雄太 九州大学, 歯学研究院, 助教 (80759746) ; 山座 治義 九州大学, 歯学研究院, 准教授 (30336151) ; 増田 啓次 九州大学, 大学病院, 講師 (60392122) ; 野中 和明 九州大学, 歯学研究院, 教授 (90128067)
• Research Collaborator: Meno Chikara
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 口唇裂口蓋裂 / 酸化ストレス / ミトコンドリア / 葉酸

Outline of Final Research Achievements

The incidence of cleft lip and palate is extremely high at 1 in 700 worldwide. Although the development of preventive methods is urgently needed, the pathogenesis of cleft lip and palate has not been sufficiently clarified and effective preventive methods have not been established. Oxidative stress has previously been suggested as one of the causes of cleft lip and palate. Folic acid has been reported to prevent cleft lip and palate in epidemiological studies, possibly through its induction of antioxidative stress. Therefore, in this study, we investigated the ability of folic acid to cause antioxidative stress using a cellular model of neural crest-derived stem cells that play an important role in maxillofacial formation. We demonstrated that folic acid reduces reactive oxygen species production from mitochondria and improves mitochondrial function to restore cell function.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまで葉酸の抗酸化ストレス作用機序は十分に解明されていなかったが、本研究では葉酸はミトコンドリア機能を回復させることで、抗酸化ストレス作用を発揮することを明らかにできた。葉酸摂取が口唇裂口蓋裂や神経管閉鎖障害等の先天異常を予防することが知られているが、本研究成果を通じて、葉酸摂取による先天異常予防を世間に再啓発できると考える。