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The synergistic effects of TGF-β1 and RUNX2 on enamel mineralization through regulating ODAPH expression during the maturation stage
Journal of Molecular Histology ( IF 3.2 ) Pub Date : 2022-02-14 , DOI: 10.1007/s10735-022-10060-2
Yuan Tian 1 , Haiyu Mu 1 , Zhiheng Dong 1 , Yu Wang 2 , Yuguang Gao 1 , Yan Gao 1 , Li Zhang 2
Affiliation  

Transforming growth factor β1 (TGF-β1) and Runt-related transcription factor 2 (RUNX2) are critical factors promoting enamel development and maturation. Our previous studies reported that absence of TGF-β1 or RUNX2 resulted in abnormal secretion and absorption of enamel matrix proteins. However, the mechanism remained enigmatic. In this study, TGF-β1−/−Runx2−/− and TGF-β1+/−Runx2+/− mice were successfully generated to clarify the relationship between TGF-β1 and RUNX2 during amelogenesis. Lower mineralization was observed in TGF-β1−/−Runx2−/− and TGF-β1+/−Runx2+/− mice than single gene deficient mice. Micro-computed tomography (μCT) revealed a lower ratio of enamel to dentin density in TGF-β1−/−Runx2−/− mice. Although μCT elucidated a relatively constant enamel thickness, variation was identified by scanning electron microscopy, which revealed that TGF-β1−/−Runx2−/− mice were more vulnerable to acid etching with lower degree of enamel mineralization. Furthermore, the double gene knock-out mice exhibited more serious enamel dysplasia than the single gene deficient mice. Hematoxylin–eosin staining revealed abnormalities in ameloblast morphology and arrangement in TGF-β1−/−Runx2−/− mice, which was accompanied by the absence of atypical basal lamina (BL) and the ectopic of enamel matrix. Odontogenesis-associated phosphoprotein (ODAPH) has been identified as a component of an atypical BL. The protein and mRNA expression of ODAPH were down-regulated. In summary, TGF-β1 and RUNX2 might synergistically regulate enamel mineralization through the downstream target gene Odaph. However, the specific mechanism by which TGF-β1 and RUNX2 promote mineralization remains to be further studied.



中文翻译:

TGF-β1和RUNX2通过调节成熟期ODAPH表达对牙釉质矿化的协同作用

转化生长因子 β1 (TGF-β1) 和 Runt 相关转录因子 2 (RUNX2) 是促进牙釉质发育和成熟的关键因素。我们之前的研究报道,缺乏 TGF-β1 或 RUNX2 会导致牙釉质基质蛋白的异常分泌和吸收。然而,这个机制仍然是个谜。在本研究中,成功​​生成了TGF-β1 -/- Runx2 -/-TGF-β1 +/- Runx2 ++ /-小鼠,以阐明 TGF-β1 和 RUNX2 在牙釉质形成过程中的关系。在TGF-β1 -/- Runx2 -/-TGF-β1 +/- Runx2 +/-中观察到较低的矿化小鼠比单基因缺陷小鼠。微型计算机断层扫描 (μCT) 显示TGF-β1 -/- Runx2 -/-小鼠的牙釉质与牙本质密度的比率较低。尽管 μCT 阐明了相对恒定的牙釉质厚度,但通过扫描电子显微镜发现了变化,这表明TGF-β1 -/- Runx2 -/-小鼠更容易受到酸蚀刻,牙釉质矿化程度较低。此外,双基因敲除小鼠比单基因缺陷小鼠表现出更严重的牙釉质发育不良。苏木精-伊红染色显示TGF-β1中的成釉细胞形态和排列异常-/- Runx2 -/-小鼠,伴有非典型基底层(BL)的缺失和釉质基质的异位。牙发育相关磷蛋白 (ODAPH) 已被确定为非典型 BL 的一个组成部分。ODAPH蛋白和mRNA表达下调。总之,TGF-β1 和 RUNX2 可能通过下游靶基因Odaph协同调节牙釉质矿化。然而,TGF-β1和RUNX2促进矿化的具体机制仍有待进一步研究。

更新日期:2022-02-15
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