Int J Biol Sci 2022; 18(10):3961-3980. doi:10.7150/ijbs.71390 This issue Cite

Research Paper

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

Yunlu Liu1*, Hongtao Tian1*, Yuxiang Hu1*, Yulin Cao1, Hui Song1, Shenghui Lan2,3, Zhipeng Dai4, Wei Chen5,6, Yingze Zhang5,6, Zengwu Shao1, Yong Liu1✉, Wei Tong1✉

1. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
2. Department of Orthopedics, The Eighth People's Hospital, Jiangsu University, Shanghai 200235, China.
3. Department of Orthopedics, Xuhui Branch of The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
4. Department of Orthopedics, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou 450003, Henan, China.
5. Department of Orthopedics, The Third Hospital of Hebei Medical University, Shi Jiazhuang 050051, Hebei, China.
6. NHC Key Laboratory of Intelligent Orthopedic Equipment (The Third Hospital of Hebei Medical University), Shi Jiazhuang 050051, Hebei, China.
*These authors contributed equally to the work.

Citation:
Liu Y, Tian H, Hu Y, Cao Y, Song H, Lan S, Dai Z, Chen W, Zhang Y, Shao Z, Liu Y, Tong W. Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing. Int J Biol Sci 2022; 18(10):3961-3980. doi:10.7150/ijbs.71390. https://www.ijbs.com/v18p3961.htm
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Abstract

Graphic abstract

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.

Keywords: Piezo1, Mechanosensor, PSCs, Fracture healing, YAP


Citation styles

APA
Liu, Y., Tian, H., Hu, Y., Cao, Y., Song, H., Lan, S., Dai, Z., Chen, W., Zhang, Y., Shao, Z., Liu, Y., Tong, W. (2022). Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing. International Journal of Biological Sciences, 18(10), 3961-3980. https://doi.org/10.7150/ijbs.71390.

ACS
Liu, Y.; Tian, H.; Hu, Y.; Cao, Y.; Song, H.; Lan, S.; Dai, Z.; Chen, W.; Zhang, Y.; Shao, Z.; Liu, Y.; Tong, W. Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing. Int. J. Biol. Sci. 2022, 18 (10), 3961-3980. DOI: 10.7150/ijbs.71390.

NLM
Liu Y, Tian H, Hu Y, Cao Y, Song H, Lan S, Dai Z, Chen W, Zhang Y, Shao Z, Liu Y, Tong W. Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing. Int J Biol Sci 2022; 18(10):3961-3980. doi:10.7150/ijbs.71390. https://www.ijbs.com/v18p3961.htm

CSE
Liu Y, Tian H, Hu Y, Cao Y, Song H, Lan S, Dai Z, Chen W, Zhang Y, Shao Z, Liu Y, Tong W. 2022. Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing. Int J Biol Sci. 18(10):3961-3980.

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