Swimming induces bone loss via regulating mechanical sensing pathways in bone marrow.

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.