School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, 250012, Shandong, China.
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, China.
J Mol Histol. 2018 Apr;49(2):123-131. doi: 10.1007/s10735-017-9752-1. Epub 2018 Jan 22.
Orthodontic tooth movement (OTM) is a periodontal tissue remodeling and regeneration process that is caused by bio-mechanical stimulation. This mechanical-chemical transduction process involves a variety of biological factors and signaling pathways. It has been shown that the Hippo-YAP/TAZ signaling pathway plays a pivotal role in the mechanical-chemical signal transduction process. Moreover, YAP and TAZ proteins interact with RUNX family proteins via different mechanisms. To explore the regulation of the Hippo signaling pathway during periodontal tissue remodeling, we examined the upper first molar OTM model in rats. We examined YAP, TAZ and RUNX2 expression at 12 hours, 24 hours, 2 days (2d), 4 days, 7 days (7d) and 14 days (14d) after force application. Haemotoxylin and eosin staining, immunohistochemical staining and western blot analysis were used to examine the expression level and localization of these proteins. We found that YAP, TAZ and RUNX2 expression started increasing at 2d, YAP and TAZ expression was proportional to the orthodontic force applied until peaking at 7d, and at 14d the expression started to decrease. YAP and TAZ were observed in osteocytes, bone matrix and periodontal ligament cells during OTM. Furthermore, using double labeling immunofluorescence staining, we found that the increase in TAZ expression was associated with RUNX2 expression, however, YAP and RUNX2 showed different expression patterns. These results suggest that the Hippo-YAP/TAZ signaling pathway participates in periodontal tissue remodeling through various mechanisms; TAZ may adjust bone tissue remodeling through RUNX2 during OTM, while YAP may regulate periodontal cell proliferation and differentiation.
正畸牙齿移动(OTM)是一种牙周组织重塑和再生过程,由生物力学刺激引起。这个机械-化学转导过程涉及多种生物因素和信号通路。已经表明,Hippo-YAP/TAZ 信号通路在机械-化学信号转导过程中起着关键作用。此外,YAP 和 TAZ 蛋白通过不同的机制与 RUNX 家族蛋白相互作用。为了探讨 Hippo 信号通路在牙周组织重塑过程中的调节作用,我们检查了大鼠上颌第一磨牙 OTM 模型。我们在施加力后 12 小时、24 小时、2 天(2d)、4 天、7 天(7d)和 14 天(14d)检查了 YAP、TAZ 和 RUNX2 的表达。苏木精和伊红染色、免疫组织化学染色和 Western blot 分析用于检查这些蛋白质的表达水平和定位。我们发现 YAP、TAZ 和 RUNX2 的表达在 2d 开始增加,YAP 和 TAZ 的表达与施加的正畸力成正比,直到 7d 达到峰值,然后在 14d 开始下降。在 OTM 期间,YAP 和 TAZ 观察到在成骨细胞、骨基质和牙周韧带细胞中。此外,通过双标记免疫荧光染色,我们发现 TAZ 表达的增加与 RUNX2 表达相关,然而,YAP 和 RUNX2 表现出不同的表达模式。这些结果表明,Hippo-YAP/TAZ 信号通路通过多种机制参与牙周组织重塑;TAZ 可能通过 RUNX2 在 OTM 期间调节骨组织重塑,而 YAP 可能调节牙周细胞增殖和分化。