Zhou Hang, Liu Hongzhi, Lin Minmin, Wang Hantang, Zhou Jingjing, Li Ming, Yang Xue, Fu Guibing, Liu Chao
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.
J Orthop Translat. 2024 Jul 25;48:11-24. doi: 10.1016/j.jot.2024.07.001. eCollection 2024 Sep.
Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear.
Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1 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.
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.
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.
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.
高压氧（HBO）疗法被广泛用于治疗骨缺损，但高氧浓度和压力与骨生成之间的相关性尚不清楚。
对12周龄的Prrx1-Cre; Rosa26-tdTomato和Prrx1-Cre; Piezo1小鼠进行双侧单皮质胫骨缺损手术。术后第1天至第9天每天进行HBO治疗；术后第5天至第8天每天对胫骨进行机械加载。在术后第10天对小鼠实施安乐死，并使用μCT、生物力学测试和免疫荧光深部组织成像评估其胫骨的骨缺损修复情况。通过空间相关性分析确定血管生成-骨生成耦合程度。对基因敲除小鼠的骨髓基质细胞进行体外培养，并评估这些细胞的成骨能力。使用RNA测序和定量实时聚合酶链反应评估Piezo1-YAP途径中基因的激活情况。
谱系追踪显示，HBO疗法显著改变了愈合骨缺损中Prrx1细胞及其后代的数量。使用条件性基因敲低小鼠，我们发现HBO刺激激活了Prrx1细胞中的Piezo1-YAP轴，并在骨修复过程中促进骨生成-血管生成耦合。HBO的有益作用与合成代谢机械刺激相似，后者也通过Piezo1-YAP轴起作用。随后的转录组测序结果显示，HBO疗法在骨缺损中激活了类似的机械敏感途径。
HBO疗法通过Prrx1成骨祖细胞群体中的机械敏感Piezo1-YAP途径促进骨组织再生。我们的研究结果有助于理解HBO疗法治疗骨缺损的机制。
高压氧疗法在临床环境中被广泛应用。我们的研究结果表明，HBO刺激后，骨祖细胞中Piezo1-YAP途径的激活诱导了骨生成，并阐明了其潜在机制。这些结果可能有助于改进当前的HBO方法，并导致制定出能实现相同功能结果的替代治疗方案。
