Department of Orthodontics, University Medical Center Hamburg, Hamburg, Germany.
Department of Orthodontics, University of Leipzig Medical Center, Leipzig, Germany.
J Dent Res. 2021 Dec;100(13):1501-1509. doi: 10.1177/00220345211012386. Epub 2021 May 19.
The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a inducible transgenic mouse model targeting -expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro-computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of expression and a 3-fold increased bone volume after 9 wk of expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of expression. However, 9 wk of expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of expression revealed that expression affects mandibular bone and growing incisors but not molar teeth, indicating that influences only growing tissues. To further investigate the effect of on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing -HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry.
WNT/β-连环蛋白信号通路在牙周生物学中起着核心作用，但特定的细胞外 WNT 配体的功能仍知之甚少。通过使用一种靶向表达牙槽骨成骨细胞、成牙本质细胞和牙骨质细胞的诱导型转基因小鼠模型，我们证明 WNT 配体 WNT1 是体内牙骨质和牙槽骨形成的强有力启动子。我们在 Wnt1Tg 小鼠中诱导表达 1、3 或 9 周，并在 6 周和 12 周时对其进行分析。下颌骨的微计算机断层扫描 (CT) 分析显示，与对照组相比，表达后的 1 和 3 周骨体积增加了 1.8 倍，表达后的 9 周骨体积增加了 3 倍。此外，与对照组相比，Wnt1Tg 小鼠的牙槽嵴更高。非脱钙组织学显示，表达后 3 周和 9 周时无细胞牙骨质厚度和细胞牙骨质体积增加。然而，表达 9 周也与牙周破坏和牙髓异位矿化有关。通过定量背散射电子成像和非胶原蛋白的免疫组织化学分析，这种异位基质的组成与细胞牙骨质相似。我们对表达后 9 周的 52 周龄小鼠的分析表明，表达影响下颌骨和生长中的切牙，但不影响磨牙，这表明仅影响生长中的组织。为了进一步研究对牙骨质细胞的影响，我们用表达 -HA 的载体稳定转染牙骨质细胞系 (OCCM-30)，并进行了增殖和分化实验。这些实验表明，促进了牙骨质细胞的增殖，但不能促进其分化。总之，我们的研究结果首次确定了作为牙槽骨和牙骨质形成的关键调节因子，并为再生牙科中利用 WNT 信号通路提供了重要的见解。
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