Abstract
Osteonecrosis of the femoral head (ONFH) frequently occurs after glucocorticoid (GC) treatment. Extracellular vesicles (EVs) are important nano-sized paracrine mediators of intercellular crosstalk. Herein, we found that intravenous administration of EVs from human urine-derived stem cells (USC-EVs) at the early stage of GC exposure rescues angiogenesis impairment, reduces apoptosis of bone marrow and trabecular bone cells, prevent trabecular bone destruction and improves bone microarchitecture in the femoral heads of rats. In vitro, USC-EVs reverse GC-induced suppression of endothelial angiogenesis and activation of cellular apoptosis. Deleted in malignant brain tumors 1 (DMBT1) and tissue inhibitor of metalloproteinases 1 (TIMP1) are enriched in USC-EVs and essential for USC-EVs-induced pro-angiogenic and anti-apoptotic effects in GC-treated cells, respectively. Knockdown of TIMP1 in USC-EVs attenuates their protective effects against GC-induced ONFH. Our study suggests that USC-EVs are a novel promising nano-sized agent for the prevention of GC-induced ONFH by delivering pro-angiogenic DMBT1 and anti-apoptotic TIMP1.
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