ラットにおける実験的な未熟歯の移動において、Notchシグナル伝達の阻害が歯根吸収を抑制することを示している

Notch signaling inhibition protects against root resorption in experimental immature tooth movement in rats.

• Xinyi Li
• Jingchen Xu
• Yuanyuan Yin
• Ting Liu
• Le Chang
• Shushu He
• Song Chen

抄録

はじめに:

本研究では、実験的に未熟な歯の移動モデルを構築し、同じ矯正治療中に未発達の歯根が完全に発達した歯根に比べて吸収が少ないことを検証し、その細胞・分子メカニズムを検討することを目的とした。

INTRODUCTION: This study aimed to build an experimental immature tooth movement model and verify less resorption of incompletely developed roots than those fully developed during the same orthodontic treatment, followed by investigating the cellular and molecular mechanism.

方法:

Wistarラットの歯の発生をインビボマイクロコンピュータ断層撮影とヘマトキシリン・エオジン染色を用いて調べ、未熟歯群と成熟歯群のラットの適齢期を決定した。未熟歯群と成熟歯群のラットを実験群、シャムコントロール群、ブランクコントロール群に分けた。矯正治療を3週間行った後、マイクロコンピュータ断層撮影法を用いて、歯間根量、歯冠移動距離、歯頸部移動距離、歯根傾斜、歯先距離を測定した。TRAP、Jagged1、Notch2、IL-6、RANKLの発現を免疫組織化学染色およびリアルタイムポリメラーゼ連鎖反応により解析した。また、歯列矯正力を3週間と6週間除去した後の歯根吸収の修復についても調べた。

METHODS: The development of Wistar rat tooth was investigated using in vivo microcomputed tomography and hematoxylin and eosin staining to decide the optimal ages of rats for immature tooth and mature tooth groups. The rats in the immature tooth and mature tooth groups were divided into experimental, sham control, and blank control groups. After orthodontic treatment for 3 weeks, the mesial root volume, crown movement distance, neck movement distance, root inclination, and apical distance were measured by microcomputed tomography. The expressions of TRAP, Jagged1, Notch2, IL-6, and RANKL were analyzed by immunohistochemical staining and real-time polymerase chain reaction. The repair of root resorption was also investigated after removing orthodontic force for 3 and 6 weeks.

結果:

根は10週齢頃に発育期を迎えたため，未熟歯群には4週齢ラットを，成熟歯群には10週齢ラットを用いた．その結果，未熟歯群の根吸収量は0.0869±0.0.0244mmであり，成熟歯群（0.1218±0.0123mm）よりも少なかった（P＜0.001）．未熟な歯の移動は、破骨細胞には統計的に有意な影響を及ぼさないが、圧迫側のTRAP陽性のオドントクラストを減少させた。成熟歯群のJagged1, Notch2, IL-6, RANKLのタンパク質発現は未熟歯群に比べて有意に増加し，圧縮側だけでなく緊張側でも発現が認められた．Jagged1、Notch2、RANKLのmRNA発現は未熟歯群で有意に低かったのに対し、IL-6の発現は有意ではなかったが強い傾向が見られた。また，3週間の修復後の根の体積はブランク群に比べて減少していたが，6週間の修復後ではその差は統計的に有意ではなかった．

RESULTS: The root achieved the development stage around 10 weeks, so 4-week-old rats and 10-week-old rats were used in the immature tooth group and mature tooth group, respectively. The volume of root resorption in the experimental immature tooth group was 0.0869 ± 0.0244 mm, which was less than that in the mature tooth group (0.1218 ± 0.0123 mm) (P <0.001). Immature tooth movement decreased TRAP-positive odontoclasts on the compression side while having no statistically significant effect on osteoclasts. The protein expression of Jagged1, Notch2, IL-6, and RANKL in the mature tooth group increased significantly compared with the immature tooth group, not only on the compression side but also on the tension sides. The mRNA expression of Jagged1, Notch2, and RANKL was significantly lower in the immature tooth group, whereas the expression of IL-6 had no significance but a strong tendency. The root volume after repairing for 3 weeks was still less than that of blank control, whereas after repairing for 6 weeks, the difference was not statistically significant.

結論:

Wistarラットを用いた実験的な未熟歯移動モデルを初めて達成しました。これは、Jagged1/Notch2/IL-6/RANKL シグナルの発現低下による歯根吸収の抑制によるものと考えられます。

CONCLUSIONS: The experimental immature tooth movement model for the Wistar rat was achieved for the first time. The immature tooth will suffer less root resorption than the mature tooth, which may be due to odontoclastogenesis inhibition by decreased expression of Jagged1/Notch2/IL-6/RANKL signaling.

Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.