Abstract
Pulsed electromagnetic fields (PEMFs) enhance bone formation to combat osteoporosis, yet the mechanisms by which they promote bone health during aging remain unclear. This study shows PEMFs enhance new bone formation and innervation, promoting osteogenesis and reducing adipogenesis in mesenchymal stem cells (MSCs) in aging male mice. PEMF-induced osteogenesis is impaired by sensory nerve dysfunction in this model. Mechanistically, PEMFs stimulate sensory nerves to secrete semaphorin 3A (Sema3A), and depleting these nerves or knocking out Sema3a eliminates PEMFs' bone-forming effects. Sema3A interacts with neuropilin-1 (Nrp1) in MSCs that express the leptin receptor, aiding osteogenesis and inhibiting adipogenesis in aging male mice. The activation of the "Sema3A-Nrp1" pathway is central for the anti-senescence effects of PEMFs on MSCs, and knocking out Nrp1 in MSCs that express the leptin receptor negates PEMFs' benefits. Overall, PEMFs stimulate sensory nerves to produce Sema3A, which promotes osteogenesis, inhibits adipogenesis, and counters MSC senescence. This underscores their therapeutic potential for treating osteoporosis in aging males.