Roles and mechanisms of YAP/TAZ in orthodontic tooth movement

Deng, Lanzhi; Chen, Yilin; Guo, Jiusi; Han, Xianglong; Guo, Yongwen

doi:10.1002/jcp.30388

Cited by 9 publications

(7 citation statements)

References 74 publications

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“…F-actin staining showed that LIPUS affected cytoskeletal structural through EphrinB2/EphB4. Hippo pathway is a mechanical stress sensing pathway closely related to the cytoskeleton; participates in the modulation of periodontal homeostasis (Deng et al, 2021). It has been reported that PDLCs sense and respond to mechanical forces during OTM with YAP (Huelter-Hassler et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling

Zhou

Zhu

et al. 2023

Front. Bioeng. Biotechnol.

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Background: The limited regenerative potential of periodontal tissue remains a challenge in orthodontic treatment, especially with respect to alveolar bone remodeling. The dynamic balance between the bone formation of osteoblasts and the bone resorption of osteoclasts controls bone homeostasis. The osteogenic effect of low-intensity pulsed ultrasound (LIPUS) is widely accepted, so LIPUS is expected to be a promising method for alveolar bone regeneration. Osteogenesis is regulated by the acoustic mechanical effect of LIPUS, while the cellular perception, transduction mode and response regulation mechanism of LIPUS stimuli are still unclear. This study aimed to explore the effects of LIPUS on osteogenesis by osteoblast-osteoclast crosstalk and the underlying regulation mechanism.Methods: The effects of LIPUS on orthodontic tooth movement (OTM) and alveolar bone remodeling were investigated via rat model by histomorphological analysis. Mouse bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes (BMMs) were purified and used as BMSC-derived osteoblasts and BMM-derived osteoclasts, respectively. The osteoblast-osteoclast co-culture system was used to evaluate the effect of LIPUS on cell differentiation and intercellular crosstalk by Alkaline phosphatase (ALP), Alizarin Red S (ARS), tartrate-resistant acid phosphatase (TRAP) staining, real-time quantitative PCR, western blotting and immunofluorescence.Results: LIPUS was found to improve OTM and alveolar bone remodeling in vivo, promote differentiation and EphB4 expression in BMSC-derived osteoblasts in vitro, particularly when cells were directly co-cultured with BMM-derived osteoclasts. LIPUS enhanced EphrinB2/EphB4 interaction between osteoblasts and osteoclasts in alveolar bone, activated the EphB4 receptor on osteoblasts membrane, transduced LIPUS-related mechanical signals to the intracellular cytoskeleton, and gave rise to the nuclear translocation of YAP in Hippo signaling pathway, thus regulating cell migration and osteogenic differentiation.Conclusions: This study shows that LIPUS modulates bone homeostasis by osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling, which benefits the balance between OTM and alveolar bone remodeling.

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Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling

Zhou

Zhu

et al. 2023

Front. Bioeng. Biotechnol.

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“…A recent study has also demonstrated the roles and mechanisms of the YAP/TAZ pathway in the orthodontic force transduction. YAP and TAZ are capable of reading mechanical cues, such as shear stress, cell shape, and extracellular matrix rigidity, and stimulate downstream cellular activity ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamic alternations of RANKL/OPG ratio expressed by cementocytes in response to orthodontic‑induced external apical root resorption in a rat model

et al. 2022

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The aim of the present study was to investigate the alterations in the formation of cementocytes in response to orthodontic forces and to evaluate the contribution of these cells in the biological changes of tooth movement and associated root resorption. A total of 90 Sprague Dawley rats were randomly assigned to the control, high force, and low force groups. Intrusion forces of 10 and 50 g were applied on the rat molar to induce tooth intrusion. The tooth movement was observed from 0 to 14 days by micro-computed tomography, bone histometric analysis, tartrate-resistant acid phosphatase staining, as well as reverse transcription-quantitative PCR and immunofluorescence staining assays. The results suggested that under low force conditions, osteoclasts were distributed at a higher frequency on the bone side than on the root side. Under high force conditions, both sides suffered osteoclast infiltration. In the low force group, the cementocytes exhibited downregulated sclerostin ( SOST ) and osteoprotegerin ( OPG ) mRNA levels and a lower receptor activator of nuclear factor-κB ligand ( RANKL )/ OPG ratio over a certain period of time. The expression levels of these genes were lower compared with those of the osteocytes at each time-point. In the high force group, both cementocytes and osteocytes upregulated the SOST and RANKL/OPG ratio on days 7 and 14, while the cementocytes expressed higher levels of SOST mRNA than those noted in the osteocytes. These data suggested that cementocytes responded to the orthodontic force via modulation of the RANKL/OPG ratio and SOST expression. The biological response of cementocytes contributed to the mechanotransduction and homoeostasis of the roots under compression. Excessive forces may act as a negative factor of this regulatory role. These results expand our knowledge on the function of cementocytes.

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“…Recent studies have revealed that cells exhibit various biological reactions when exposed to different forces ( Huang et al, 2018 ), including mechanical forces such as continuous or intermittent compression forces, fluid shear force, mechanical vibration, cyclic tension stress, and static tensile strain ( Chen et al, 2021 ; Qin et al, 2021 ; Wu et al, 2021 ; Shi et al, 2022 ; Sun et al, 2022 ; Manokawinchoke et al, 2023 ). Mechanical force–induced OTM leads to a series of cell proliferation, differentiation, and apoptosis in periodontal tissues ( Deng et al, 2021 ). Periodontal ligament fibroblasts (PDLFs, the main cellular component of PDLCs, also known as PDLCs ( Li et al, 2021 )) provide the biological basis for periodontal soft tissue remodeling through myofibroblast differentiation.…”

Section: Yap and Taz Regulate Periodontal Homeostasis And Remodelingmentioning

confidence: 99%

Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis

Ma,

Fan,

Geng

2024

Front. Cell Dev. Biol.

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Orthodontic tooth movement (OTM) involves mechanical–biochemical signal transduction, which results in tissue remodeling of the tooth–periodontium complex and the movement of orthodontic teeth. The dynamic regulation of osteogenesis and osteoclastogenesis serves as the biological basis for remodeling of the periodontium, and more importantly, the prerequisite for establishing periodontal homeostasis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key effectors of the Hippo signaling pathway, which actively respond to mechanical stimuli during tooth movement. Specifically, they participate in translating mechanical into biochemical signals, thereby regulating periodontal homeostasis, periodontal remodeling, and tooth development. YAP and TAZ have widely been considered as key factors to prevent dental dysplasia, accelerate orthodontic tooth movement, and shorten treatment time. In this review, we summarize the functions of YAP and TAZ in regulating tooth development and periodontal remodeling, with the aim to gain a better understanding of their mechanisms of action and provide insights into maintaining proper tooth development and establishing a healthy periodontal and alveolar bone environment. Our findings offer novel perspectives and directions for targeted clinical treatments. Moreover, considering the similarities and differences in the development, structure, and physiology between YAP and TAZ, these molecules may exhibit functional variations in specific regulatory processes. Hence, we pay special attention to their distinct roles in specific regulatory functions to gain a comprehensive and profound understanding of their contributions.

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Roles and mechanisms of YAP/TAZ in orthodontic tooth movement

Cited by 9 publications

References 74 publications

Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling

Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling

Dynamic alternations of RANKL/OPG ratio expressed by cementocytes in response to orthodontic‑induced external apical root resorption in a rat model

Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis

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