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通过抑制音猬因子信号通路来恢复小鼠双套牙列的形成

Revitalizing mouse diphyodontic dentition formation by inhibiting the sonic hedgehog signaling pathway.

作者信息

Mao Chuanqing, Lai Yongzhen, Liao Caiyu, Chen Jiangping, Hong Yuhang, Ren Chengyan, Wang Chengyong, Lu Meng, Chen Weihui

机构信息

Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Fujian Key Laboratory of Oral Diseases & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.

出版信息

Dev Dyn. 2022 May;251(5):759-776. doi: 10.1002/dvdy.436. Epub 2021 Nov 9.

Abstract

BACKGROUND

Tooth regeneration depends on the longevity of the dental epithelial lamina. However, the exact mechanism of dental lamina regression has not yet been clarified. To explore the role of the Sonic hedgehog (Shh) signaling pathway in regression process of the rudimentary successional dental lamina (RSDL) in mice, we orally administered a single dose of a Shh signaling pathway inhibitor to pregnant mice between embryonic day 13.0 (E13.0) and E17.0.

RESULTS

We observed that the Shh signaling pathway inhibitor effectively inhibited the expression of Shh signaling pathway components and revitalized RSDL during E15.0-E17.0 by promoting cell proliferation. In addition, mRNA-seq, reverse transcription plus polymerase chain reaction (RT-qPCR), and immunohistochemical analyses indicated that diphyodontic dentition formation might be related to FGF signal up-regulation and the Sostdc1-Wnt negative feedback loop.

CONCLUSIONS

Overall, our results indicated that the Shh signaling pathway may play an initial role in preventing further development of mouse RSDL in a time-dependent manner.

摘要

背景

牙齿再生取决于牙上皮板的寿命。然而,牙板退化的确切机制尚未阐明。为了探究音猬因子(Shh)信号通路在小鼠乳牙牙板(RSDL)退化过程中的作用,我们在胚胎第13.0天(E13.0)至E17.0期间给怀孕小鼠口服单剂量的Shh信号通路抑制剂。

结果

我们观察到,Shh信号通路抑制剂在E15.0 - E17.0期间通过促进细胞增殖有效抑制了Shh信号通路成分的表达并使RSDL恢复活力。此外,mRNA测序、逆转录加聚合酶链反应(RT-qPCR)和免疫组化分析表明,双牙列的形成可能与FGF信号上调和Sostdc1-Wnt负反馈环有关。

结论

总体而言,我们的结果表明,Shh信号通路可能在以时间依赖性方式阻止小鼠RSDL的进一步发育中起初始作用。

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