Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors

Hang Zhou; Hongzhi Liu; Minmin Lin; Hantang Wang; Jingjing Zhou; Ming Li; Xue Yang; Guibing Fu; Chao Liu

Journal of Orthopaedic Translation (Sep 2024)

Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors

Hang Zhou,
Hongzhi Liu,
Minmin Lin,
Hantang Wang,
Jingjing Zhou,
Ming Li,
Xue Yang,
Guibing Fu,
Chao Liu

Affiliations

Hang Zhou: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China
Hongzhi Liu: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China
Minmin Lin: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China
Hantang Wang: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China
Jingjing Zhou: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China
Ming Li: Department of Rehabilitation Medicine, Shenzhen Children's Hospital, No. 7019 Yitian Road, Futian District, Shenzhen, Guangdong, China
Xue Yang: Department of Rehabilitation Medicine, Shenzhen Children's Hospital, No. 7019 Yitian Road, Futian District, Shenzhen, Guangdong, China; Corresponding author.
Guibing Fu: Department of Pediatric Orthopedics, Shenzhen Children's Hospital, No. 7019 Yitian Road, Futian District, Shenzhen, Guangdong, China; Corresponding author.
Chao Liu: Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China; Corresponding author. Department of Biomedical Engineering, College of Engineering, Southern University of Science and Technology, Engineering Building south 622, 1088 Xueyuan Avenue, Shenzhen, Guangdong, China.

Journal volume & issue: Vol. 48
pp. 11 – 24

Abstract

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Background: Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear. Methods: Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1fl/+ mice. Daily HBO treatment was applied on post-surgery day (PSD) 1–9; and daily mechanical loading on tibia was from PSD 5 to 8. The mice were euthanized on PSD 10, and bone defect repair in their tibias was evaluated using μCT, biomechanical testing, and immunofluorescence deep-tissue imaging. The degree of angiogenesis–osteogenesis coupling was determined through spatial correlation analysis. Bone marrow stromal cells from knockout mice were cultured in vitro, and their osteogenic capacities of the cells were assessed. The activation of genes in the Piezo1–YAP pathway was evaluated using RNA sequencing and quantitative real-time polymerase chain reaction. Results: Lineage tracing showed HBO therapy considerably altered the number of Prrx1+ cells and their progeny in a healing bone defect. Using conditional knockdown mice, we found that HBO stimulation activates the Piezo1–YAP axis in Prrx1+ cells and promotes osteogenesis–angiogenesis coupling during bone repair. The beneficial effect of HBO was similar to that of anabolic mechanical stimulation, which also acts through the Piezo1–YAP axis. Subsequent transcriptome sequencing results revealed that similar mechanosensitive pathways are activated by HBO therapy in a bone defect. Conclusion: HBO therapy promotes bone tissue regeneration through the mechanosensitive Piezo1–YAP pathway in a population of Prrx1+ osteogenic progenitors. Our results contribute to the understanding of the mechanism by which HBO therapy treats bone defects. The Translational Potential of this Article: Hyperbaric oxygen therapy is widely used in clinical settings. Our results show that osteogenesis was induced by the activation of the Piezo1–YAP pathway in osteoprogenitors after HBO stimulation, and the underlying mechanism was elucidated. These results may help improve current HBO methods and lead to the formulation of alternative treatments that achieve the same functional outcomes.

Published in Journal of Orthopaedic Translation

ISSN: 2214-031X (Print); 2214-0328 (Online)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: http://www.journals.elsevier.com/journal-of-orthopaedic-translation/

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