Mechanical Force-Induced Macrophage Mitochondrial Dynamics Changes In Regulating Osteogenesis

This study aims to clarify the role and mechanism by which mechanical tensile forces regulate the bone immune microenvironment through alterations in macrophage mitochondrial dynamics. We employed a cellular tension loading system and found that mechanical tension altered mitochondrial dynamics in macrophages, leading to increased mitochondrial fission. Using a macrophages-BMSCs direct co-culture system, we demonstrated that macrophages transferred mitochondria to BMSCs, a process enhanced by mechanical tension. 1) Mechanical stretching altered macrophage mitochondrial dynamics, causing mitochondrial fragmentation, increased membrane potential, and enhanced transfer to BMSCs. 2) Mechanical stretch led to the recruitment of DRP1 from the cytoplasm to mitochondria in macrophages, and silencing DRP1 reduced the promotion of mitochondrial transfer by mechanical forces. 3) Mitochondria-rich extracellular vesicles (Mito-EVs) secreted by stretched macrophages interacted with the CD200 receptor on BMSCs, promoting osteogenic differentiation of BMSCs and enhancing bone formation in mice. Mechanical tensile forces induce macrophage mitochondrial dynamic changes via the activation of DRP1, promoting mitochondrial fragmentation and transfer through Mito-EVs to BMSCs. This process regulates the metabolic reprogramming of BMSC mitochondria via the CD200R-CD200 pathway, activating their differentiation into osteoblasts and accelerating bone formation in vivo.