Expression pattern of YAP and TAZ during orthodontic tooth movement in rats

Abstract

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.

TAZ contributes to osteogenic differentiation of periodontal ligament cells under tensile stress

“…In consistence with the abovementioned investigations, the present study revealed that CTS‐induced osteogenic differentiation of PDLCs via the activation of TAZ, as evidenced by the enhanced expression and nucleus localization of TAZ and its binding with Cbfα1. Moreover, our results further extended the in vivo immunohistochemistry findings from rats with OTM, in which TAZ co‐localize with Cbfα1 on both tension and compression side of the periodontal tissues …”

“…ent study revealed that CTS-induced osteogenic differentiation of PDLCs via the activation of TAZ, as evidenced by the enhanced expression and nucleus localization of TAZ and its binding with Cbfα1.Moreover, our results further extended the in vivo immunohistochemistry findings from rats with OTM, in which TAZ co-localize with Cbfα1 on both tension and compression side of the periodontal tissues 14. Although it has been well established that the canonical Wnt/β-catenin signaling is of great importance for mechanosensation and mechanotransduction in osteogenic commitment of osteocytes,[28][29][30] there still exists limited evidence with regard to F I G U R E 1 Cyclic tensile stress induces the osteogenic differentiation of PDLCs.…”

“…The osteogenic activity of TAZ has been confirmed to be induced by both mechanical and chemical stimuli; however, whether tensile strain contributes to osteogenesis via activation of TAZ remains unclear. Notably, a very recent study indicated that TAZ could co‐locate with Cbfα1 in periodontal ligaments during OTM in murine models, suggesting the possible role of TAZ in orthodontic bone remodeling . Additionally, TAZ is closely associated with Wnt/β‐catenin signaling, the activation of which accounts for the osteogenic differentiation of human PDLCs under mechanical loading .…”

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

“…Previous studies reported that activation of YAP could induce osteogenic differentiation in MSCs [ 1 , 24 ]. Xu et al proved that YAP/TAZ was involved in the process of periodontal tissue remodeling during OTM in rat [ 25 ]. Furthermore, they demonstrated that knockdown of YAP induced the apoptosis and inhibited the proliferation of human periodontal ligament stem cells (h-PDLSCs) through crosstalk between Erk and Bcl-2 signaling pathway, suggesting that YAP signaling pathway participated in regulating biological behaviors of h-PDLSCs [ 26 ].…”

Traumatic occlusion aggravates bone loss during periodontitis and activates Hippo‐YAP pathway

“…We further stimulated fibroblasts and pre‐osteoblasts with cyclic force to confirm our in vivo results and observed significant activation of Hippo‐YAP pathway upon abnormal stress transmission. In previous studies, YAP and TAZ were shown to be associated with tissue regeneration (Huelter‐Hassler, Tomakidi, Steinberg, & Jung, ; Sun et al., ; Zheng et al., ). In our study, OE aggravated bone loss caused by P.g colonization, while the OE only group did not show severe bone loss and osteoclastic activity, consistent with previous research.…”