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

Area of Science:

• Bone biology
• Mechanobiology
• Cellular signaling

Background:

• Bone dynamically responds to mechanical stress via mechanosensing proteins (e.g., Piezo1, YAP/TAZ).
• High-load exercise promotes bone formation, but low-load exercise effects on bone homeostasis remain unclear.
• Bone marrow cells are mobilized and influenced by mechanical signals.

Purpose of the Study:

• To investigate the effects of long-term low-load mechanical stress on bone homeostasis.
• To identify molecular and cellular changes in the bone marrow microenvironment induced by unloading.
• To elucidate the role of specific signaling pathways and cell types in response to mechanical unloading.

Main Methods:

• Established a long-term swimming training model in mice to induce mechanical unloading.
• Utilized microCT scanning and histological staining to assess bone mass.
• Performed single-cell sequencing on tibial bone marrow tissue.
• Analyzed gene expression profiles, focusing on Integrins and the ERK1/2 signaling pathway.

Main Results:

• Swimming training led to significant loss of trabecular bone mass.
• Single-cell sequencing revealed an increased percentage of bone marrow neutrophils.
• Alterations in Integrins and the ERK1/2 signaling pathway were observed, particularly pronounced in macrophages.
• Integrins were identified as critical for monocyte precursor and macrophage crosstalk during swimming.

Conclusions:

• Long-term swimming-induced unloading negatively impacts bone mass.
• Bone marrow cell gene expression profiles are significantly altered by swimming.
• Integrins and the ERK1/2 signaling pathway play crucial roles in the bone marrow's adaptive response to mechanical unloading.