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Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periostea...

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Autores principales: Liu, Yunlu, Tian, Hongtao, Hu, Yuxiang, Cao, Yulin, Song, Hui, Lan, Shenghui, Dai, Zhipeng, Chen, Wei, Zhang, Yingze, Shao, Zengwu, Liu, Yong, Tong, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274506/
https://www.ncbi.nlm.nih.gov/pubmed/35844802
http://dx.doi.org/10.7150/ijbs.71390
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author Liu, Yunlu
Tian, Hongtao
Hu, Yuxiang
Cao, Yulin
Song, Hui
Lan, Shenghui
Dai, Zhipeng
Chen, Wei
Zhang, Yingze
Shao, Zengwu
Liu, Yong
Tong, Wei
author_facet Liu, Yunlu
Tian, Hongtao
Hu, Yuxiang
Cao, Yulin
Song, Hui
Lan, Shenghui
Dai, Zhipeng
Chen, Wei
Zhang, Yingze
Shao, Zengwu
Liu, Yong
Tong, Wei
author_sort Liu, Yunlu
collection PubMed
description The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of β-catenin. In detail, YAP directly interacts with β-catenin in the nucleus and forms a transcriptional YAP/β-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion.
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spelling pubmed-92745062022-07-15 Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing Liu, Yunlu Tian, Hongtao Hu, Yuxiang Cao, Yulin Song, Hui Lan, Shenghui Dai, Zhipeng Chen, Wei Zhang, Yingze Shao, Zengwu Liu, Yong Tong, Wei Int J Biol Sci Research Paper The biomechanical environment plays a dominant role in fracture healing, and Piezo1 is regarded as a major mechanosensor in bone homeostasis. However, the role of Piezo1 in fracture healing is not yet well characterized. In this study, we first delineated that Piezo1 is highly expressed in periosteal stem cells (PSCs) and their derived osteoblastic lineage cells and chondrocytes. Furthermore, downregulation of Piezo1 in callus leads to impaired fracture healing, while activation by its specific agonist promotes fracture healing through stimulation of PSC-modulated chondrogenesis and osteogenesis, along with accelerated cartilage-to-bone transformation. Interestingly, vascular endothelial growth factor A is upregulated after Yoda1 treatment of PSCs, indicating an indirect role of Piezo1 in angiogenesis. Mechanistically, activation of Piezo1 promotes expression of Yes-associated protein (YAP) and its nuclear localization in PSCs, which in turn increases the expression and nuclear localization of β-catenin. In detail, YAP directly interacts with β-catenin in the nucleus and forms a transcriptional YAP/β-catenin complex, which upregulates osteogenic, chondrogenic and angiogenic factors. Lastly, Yoda1 treatment significantly improves fracture healing in a delayed union mouse model generated by tail suspension. These findings indicate that Piezo1 is a potential therapeutic target for fracture delayed union or nonunion. Ivyspring International Publisher 2022-06-13 /pmc/articles/PMC9274506/ /pubmed/35844802 http://dx.doi.org/10.7150/ijbs.71390 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Liu, Yunlu
Tian, Hongtao
Hu, Yuxiang
Cao, Yulin
Song, Hui
Lan, Shenghui
Dai, Zhipeng
Chen, Wei
Zhang, Yingze
Shao, Zengwu
Liu, Yong
Tong, Wei
Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title_full Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title_fullStr Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title_full_unstemmed Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title_short Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing
title_sort mechanosensitive piezo1 is crucial for periosteal stem cell-mediated fracture healing
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274506/
https://www.ncbi.nlm.nih.gov/pubmed/35844802
http://dx.doi.org/10.7150/ijbs.71390
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