Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Oral Dis. 2022 Mar;28(2):442-451. doi: 10.1111/odi.13753. Epub 2021 Jan 16.
In this study, we attempted to define the precise window of time for molar root elongation using a gain-of-function mutation of β-catenin model.
Both the control and constitutively activated β-catenin (CA-β-cat) mice received a one-time tamoxifen administration (for activation of β-catenin at newborn, postnatal day 3, or 5, or 7, or 9) and were harvested at the same stage of P21. Multiple approaches were used to define the window of time of postnatal tooth root formation.
In the early activation groups (tamoxifen induction at newborn, or P3 or P5), there was a lack of molar root elongation in the CA-β-cat mice. When induced at P7, the root length was slightly reduced at P21. However, the root length was essentially the same as that in the control when β-cat activated at P9. This study indicates that root elongation occurs in a narrow time of window, which is highly sensitive to a change of β-catenin levels. Molecular studies showed a drastic decrease in the levels of nuclear factor I-C (NFIC) and osterix (OSX), plus sharp reductions of odontoblast differentiation markers, including Nestin, dentin sialoprotein (DSP), and dentin matrix protein 1 (DMP1) at both mRNA and protein levels.
Murine molar root elongation is precisely regulated by the Wnt/β-catenin signaling within a narrow window of time (newborn to day 5).
在本研究中，我们试图通过β-连环蛋白功能获得突变模型来定义磨牙牙根伸长的确切时间窗。
对照组和组成型激活β-连环蛋白（CA-β-cat）小鼠均接受单次他莫昔芬给药（在新生、出生后第 3、5、7 或 9 天激活β-连环蛋白），并在 P21 相同阶段收获。采用多种方法来定义出生后牙齿根部形成的时间窗。
在早期激活组（新生或 P3 或 P5 时他莫昔芬诱导），CA-β-cat 小鼠的磨牙牙根伸长缺乏。当在 P7 诱导时，在 P21 时根长略有减少。然而，当β-cat 在 P9 激活时，根长与对照组基本相同。本研究表明，牙根伸长发生在一个狭窄的时间窗内，对β-连环蛋白水平的变化高度敏感。分子研究表明，核因子 I-C（NFIC）和骨形成蛋白 2（OSX）的水平急剧下降，牙本质涎蛋白（DSP）和牙本质基质蛋白 1（DMP1）的成牙本质分化标志物的表达在 mRNA 和蛋白质水平均明显降低。
鼠磨牙牙根伸长受 Wnt/β-连环蛋白信号在狭窄时间窗（新生至第 5 天）内的精确调控。
