Enhancing Osteogenesis in Osteoporosis via Electromagnetized Gold Nanoparticles.

Osteoporosis (OP) is the most common bone metabolic disorder worldwide, markedly compromising patients' quality of life and imposing a substantial healthcare burden. However, current clinical treatments for OP are not able to provide satisfactory therapeutic outcomes, particularly in the presence of complex inflammatory conditions. The integration of noninvasive physical therapy and bionanotechnology has shown great promise in modulating cellular functions and optimizing the bone microenvironment. In this study, we demonstrated that electromagnetized gold nanoparticles (AuNPs) exhibited excellent biocompatibility at the cellular, vascular, and major organ levels. These electromagnetized AuNPs significantly enhanced the biological behaviors of osteoblasts, including proliferation, migration, colony formation, and osteogenic differentiation. Remarkably, RNA sequencing analysis revealed that electromagnetized AuNPs significantly activated the mitochondrial oxidative phosphorylation pathway while suppressing the interleukin-17 pro-inflammatory signaling pathway. Additionally, electromagnetized AuNPs stabilized mitochondrial membrane potential and boosted adenosine triphosphate (ATP) production while reducing cell apoptosis and oxidative stress, thereby promoting osteogenic differentiation under inflammatory conditions. Furthermore, in a mouse model of inflammation-induced OP, the electromagnetized AuNPs effectively restored bone mass and improved trabecular architecture. Collectively, our findings provide a proof-of-concept that electromagnetized AuNPs enhance osteogenesis by promoting osteogenic differentiation and optimizing the bone microenvironment, highlighting their potential as a promising therapeutic strategy for OP.