Pulsed electromagnetic field drives osteogenic and suppresses adipogenic differentiation of bone marrow mesenchymal stem cells <i>via</i> Wnt/β-catenin signaling to ameliorate osteoporosis.

Abstract

A pathological shift in bone marrow mesenchymal stem cell (BMSC) differentiation towards adipogenesis at the expense of osteogenesis is a key cellular driver of osteoporosis induced by glucocorticoids or estrogen deficiency. Pulsed electromagnetic field (PEMF) therapy shows clinical promise for bone disorders, yet its capacity to directly correct this lineage imbalance and the specific molecular mechanisms involved remain insufficiently defined. Here, we demonstrate that PEMF (75 Hz, 1.5 mT) directly counteracts dexamethasone (Dex)-induced effects in rat BMSCs, promoting osteogenic differentiation and concurrently suppressing adipogenesis <i>in vitro</i>. Mechanistically, PEMF activates the canonical Wnt/β-catenin pathway, evidenced by β-catenin nuclear translocation and upregulation of target genes (Axin2, LEF-1). The functional necessity of this pathway was confirmed using the pharmacological inhibitor XAV-939, which completely abrogated PEMF's pro-osteogenic and anti-adipogenic effects. In ovariectomized (OVX) rats, daily PEMF exposure for 8 weeks significantly preserved trabecular bone mass and microarchitecture, enhanced bone formation rate, and reduced bone marrow adiposity. Critically, <i>in vivo</i> co-administration of XAV-939 markedly attenuated these therapeutic benefits. Our findings establish that PEMF ameliorates osteoporosis by acting as a physical activator of the Wnt/β-catenin pathway in BMSCs, thereby rectifying their differentiation bias, and present a novel mechanism-based non-invasive strategy.