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.
Hippo signaling pathway Orthodontic tooth movement (OTM) Yes-Associated Protein (YAP) Transcriptional Co-activator with PDZ-binding Domain (TAZ) Periodontal tissue remodeling Runt Related Transcription Factor 2 (RUNX2)
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This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81300885), Shandong Provincial key research and development program (Grant Nos. 2016GSF201115, 2016GSF201220, 2017GSF18117), Shandong Provincial Natural Science Foundation (Grant No. ZR2017MH031), China Postdoctoral Science Foundation (Grant No. 2017M610432), Young Scholars Program of Shandong University (Grant No. 2015WLJH53) and Construction Engineering Special Fund of Taishan Scholars (Grant No. ts201511106).