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

Zhou, Hang1,2; Liu, Hongzhi1,2; Lin, Minmin1,2; Wang, Hantang1,2; Zhou, Jingjing1,2; Li, Ming3; Yang, Xue3; Fu, Guibing4; Liu, Chao1,2

2024-09-01

10.1016/j.jot.2024.07.001

JOURNAL OF ORTHOPAEDIC TRANSLATION   影响因子和分区

2214-031X

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; Rosa26tdTomato 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 mu CT, 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.

Angiogenesis Bone regeneration Hyperbaric oxygenation Osteogenesis Piezo1 YAP

SCI

英语

第一 ; 通讯

Guangdong Basic and Applied Basic Research Foundation[2021A1515011447] ; Shenzhen Science and Technology Innovation Commission[KQTD20200820113012029] ; Guangdong Provincial Key Lab-oratory of Advanced Biomaterials[2022B1212010003]

Orthopedics

Orthopedics

WOS:001281283600001

ELSEVIER

Web of Science

1.Southern Univ Sci & Technol, Coll Engn, Dept Biomed Engn, Engn Bldg South 622,1088 Xueyuan Ave, Shenzhen, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Guangdong Prov Key Lab Adv Biomat, Engn Bldg South 622,1088 Xueyuan Ave, Shenzhen, Guangdong, Peoples R China
3.Shenzhen Childrens Hosp, Dept Rehabil Med, 7019 Yitian Rd, Shenzhen, Guangdong, Peoples R China
4.Shenzhen Childrens Hosp, Dept Pediat Orthoped, 7019 Yitian Rd, Shenzhen, Guangdong, Peoples R China

Zhou, Hang,Liu, Hongzhi,Lin, Minmin,et al. Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors[J]. JOURNAL OF ORTHOPAEDIC TRANSLATION,2024,48.

Zhou, Hang.,Liu, Hongzhi.,Lin, Minmin.,Wang, Hantang.,Zhou, Jingjing.,...&Liu, Chao.(2024).Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors.JOURNAL OF ORTHOPAEDIC TRANSLATION,48.

Zhou, Hang,et al."Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors".JOURNAL OF ORTHOPAEDIC TRANSLATION 48(2024).