Mechanical stretch-triggered EGR1 overexpression enhances macrophage M2 polarization and drives mitochondrial fission

Orthodontic tooth movement involves a complex interaction between mechanical forces and bone tissue remodeling. As a response to mechanical stimuli, macrophages play an important role in tissue remodeling and potential side effects. In this study, we investigated the molecular mechanism of macrophage polarization under mechanical stimulation, focusing on the dual regulation of EGR1 (Early Growth Response 1) in mitochondrial dynamics and macrophage polarization. In the cyclic stretch stress model of RAW264.7 cells in vitro, we found that mechanical tension promotes the M2 polarization phenotype of macrophages. During the first to second hour of mechanical stretching, the expression of iNOS, ARG-1, and CD163 in cells increased. At the same time, significant changes in macrophage mitochondrial dynamics include enhanced fission behavior and decreased membrane potential. The transcriptome sequencing results indicated that EGR1 was rapidly upregulated after mechanical stimulation and translocated from the cytoplasm to the nucleus. Inhibition of mitochondrial fission or knockdown of EGR1 significantly inhibited tension-induced M2 polarization. Moreover, this process may be associated with the PI3K-Akt signaling pathway. Our research findings reveal new insights into the connection between mechanical forces and macrophage function through EGR1-mediated mitochondrial dynamics. This work provides new perspectives on bone remodeling during orthodontic movement.