Abstract
Bone is an organ capable of perceiving external mechanical stress in real time and responding dynamically via mechanosensing proteins such as Piezo1 and YAP/TAZ. Upon sensing the mechano-signals, cells within the bone matrix collaborate to coordinate bone formation and resorption, while bone marrow cells are also stimulated and mobilized. High-load exercise stimulates osteoblast differentiation and bone formation. However, the mechanism through which the low-load exercises affect bone homeostasis is still unclear. In this work, we established a long-term swimming training model to unload the mechanical stress in mice. Throughout the training model, we observed a significant loss in trabecular bone mass, as evidenced by microCT scanning and histological staining. Single-cell sequencing of the tibial bone marrow tissue revealed a significant increase in the percentage of bone marrow neutrophils, along with alterations in Integrins and the ERK1/2 signaling pathway. Notably, the changes in both Integrins and the ERK1/2 signaling pathway in macrophages were more pronounced than in other cell types, which suggests a mechanical adaptive response in these cells. Moreover, the involvement of Integrins is also critical for the crosstalk between monocyte precusors and macrophages during swimming. Together, this study provides a resource of the alterations of bone marrow cell gene expression profile after swimming and highlights the importance of Integrins and the ERK1/2 signaling pathway in the bone marrow microenvironment after swimming.