Role of osteoprotegerin in the regulation of dental epithelial-mesenchymal signaling during tooth development
Role of osteoprotegerin in the regulation of dental epithelial-mesenchymal signaling during tooth development
复制标题
骨保护素在牙齿发育过程中牙上皮间质信号传导调节中的作用
DOI：
10.3892/mmr.2019.10567
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发表时间：
2019-10-01
影响因子：
3.4
通讯作者：
Xiang, Lusai
中科院分区：
文献类型：
--
作者：
Gao, Xin;Zheng, Junming;Xiang, Lusai
牙齿上皮-间充质信号传导对牙齿发育至关重要，但其详细机制尚未完全了解。利用微阵列分析，它揭示了骨保护素，一个重要的调控因子骨改建，显着增加后，去除牙上皮细胞的表达。免疫组化染色显示，在牙齿间充质内的骨保护素表达是相当低的，在产前期间，但出生后显着增加。为探讨骨保护素对牙齿发育的影响，用不同浓度的骨保护素处理胎龄14.5（E14.5）的中国昆明小鼠第一磨牙牙胚。结果显示，骨保护素可抑制牙源性标志物的表达，同时促进成骨标志物的表达，从而破坏牙齿形态发生。体外和体内培养进一步支持了这些发现。最后，定量逆转录-聚合酶链反应和免疫荧光研究显示，在骨保护素治疗后，无翅/整合（Wnt）/β-连环蛋白途径的活性增加，表明在产前牙齿发育中骨保护素表达增加可能导致Wnt/β-连环蛋白途径不受控制的上调。
Dental epithelial-mesenchymal signaling is crucial for tooth development, but the detailed mechanism is not fully understood. Using microarray analysis, it was revealed that the expression of osteoprotegerin, an important factor regulating bone remodeling, significantly increased after removal of the dental epithelium. Immunohistochemical staining revealed that osteoprotegerin expression within the dental mesenchyme was quite low during the prenatal period, but significantly increased after birth. To investigate the influence of osteoprotegerin upon tooth development, first-molar tooth germs from embryonic day 14.5 (E14.5) Chinese Kunming mice were treated with different concentrations of osteoprotegerin. It was revealed that osteoprotegerin could inhibit the expression of odontogenic markers while promoting the expression of osteogenic markers, thereby disrupting tooth morphogenesis. These findings were further supported by in vitro and in vivo cultures. Finally, quantitative reverse transcription-polymerase chain reaction and immunofluorescence studies revealed that, after osteoprotegerin treatment, the activity of the wingless/integrated (Wnt)/beta-catenin pathway increased, indicating that increased osteoprotegerin expression in prenatal tooth development could lead to uncontrolled upregulation of the Wnt/beta-catenin pathway.