Shanghai Jiao Tong University, School of Medicine, Ninth People's Hospital, Department of Endodontics and Operative Dentistry, Shanghai, China.
Tulane University, Department of Cell and Molecular Biology, New Orleans, LA, USA.
J Appl Oral Sci. 2021 Dec 13;29:e20210281. doi: 10.1590/1678-7757-2021-0281. eCollection 2021.
This study aimed to explore the precise temporospatial distributions of bone morphogenetic protein (BMP) and Wnt signaling pathways during postnatal development of mammalian tooth roots after the termination of crown morphogenesis.
A total of two transgenic mouse lines, BRE-LacZ mice and BAT-gal mice, were undertaken. The mice were sacrificed on every postnatal (PN) day from PN 3d up to PN 21d. Then, the first lower molars were extracted, and the dissected mandibles were stained with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) and fixed. Serial sections at 10 µm were prepared after decalcification, dehydration, and embedding in paraffin.
We observed BMP/Smads and Wnt/β-catenin signaling activities in the dental sac, dental pulp, and apical papilla with a certain degree of variation. The position of activation of the BMP/Smad signaling pathway was located more coronally in the early stage, which then gradually expanded as root elongation proceeded and was associated with blood vessels in the pulp and developing complex apical tissues in the later stage. However, Wnt/β-catenin signaling was highly concentrated in the mesenchyme below the cusps in the early stage, gradually expanded to regions around the root in the transition/root stage, and then disappeared entirely in the later stage.
These results further confirmed the participation of both BMP and Wnt canonical signaling pathways in tooth root development, as well as formed the basis for future studies on how precisely integrated signaling pathways regulate root morphogenesis and regeneration.
本研究旨在探索在牙冠形态发生完成后哺乳动物牙根发育过程中，骨形态发生蛋白（BMP）和 Wnt 信号通路的确切时空分布。
共进行了 2 种转基因鼠系，BRE-LacZ 鼠和 BAT-gal 鼠。从出生后第 3 天（PN3d）至第 21 天（PN21d），每天处死一批小鼠。然后，提取第一下磨牙，对解剖的下颌骨进行 5-溴-4-氯-3-吲哚基-β-d-半乳糖吡喃糖苷（X-gal）染色和固定。脱钙、脱水和石蜡包埋后，制备 10μm 厚的连续切片。
我们观察到牙囊、牙髓和根尖乳头中的 BMP/Smads 和 Wnt/β-catenin 信号活性存在一定程度的变化。BMP/Smad 信号通路的激活位置在早期更位于冠方，随着根伸长的进行逐渐扩展，并与牙髓中的血管和后期发育中的复杂根尖组织相关。然而，Wnt/β-catenin 信号在早期牙尖下方的间质中高度集中，在过渡/根阶段逐渐扩展到根周围区域，然后在后期完全消失。
这些结果进一步证实了 BMP 和 Wnt 经典信号通路都参与了牙根发育，并为未来研究精确整合的信号通路如何调节根形态发生和再生奠定了基础。
